[Pharmwaste] Can drugs found in water harm humans?

[Tenace, Laurie]

http://pubs.acs.org/subscribe/journals/esthag-w/2006/mar/science/lt_drugsinwa
ter.html

Can drugs found in water harm humans?
A mixture of pharmaceuticals at environmentally relevant concentrations is
found to inhibit the growth of human embryonic kidney cells.
Although discoveries of Prozac in drinking water and cocaine in Italian
rivers get plenty of press, little is actually known about what happens when
people are exposed to the mixtures of drugs being found in the environment.
But researchers at Italy's University of Insubria have taken an important
step. In the first study to examine the effects of a drug mixture at
environmental levels on human cells, posted today to ES&T's Research ASAP
website (DOI: 10.1021/es051715a), they report that a combination of
pharmaceutical compounds inhibits the growth of embryonic kidney cells in
laboratory tests.

Italian researchers have found pharmaceutical contaminants in the Olona
River, which flows through the city of Milan before joining the Po
River.Researchers in Europe began in the early 1990s to identify trace
amounts of certain therapeutic drugs in surface waters and groundwater. Since
then, survey campaigns in Europe and the U.S. have found about 100 such
compounds in surface waters, groundwater, sewage, effluent from wastewater
treatment plants, and even tap water-at levels as high as parts per billion.
Pharmaceutical compounds enter the environment through several different
pathways, including improper disposal and the excretion of nonmetabolized
drugs. Often, waters test positive for more than one substance.

Researchers agree that aquatic species face the greatest risk from exposure
to low levels of pharmaceuticals, such as synthetic hormones, which can act
as endocrine disrupters at environmental levels. However, little is known
about the potential human health effects arising from complex drug mixtures.

Corresponding author Franceso Pomati and his colleagues set out to fill this
gap. "To make a proper risk assessment," Pomati explains, "we needed some
data about not single drugs, taken one by one, but a mixture that was
representative of the real conditions in the environment."

The researchers designed a cocktail of 13 drugs-including several
antibiotics, the popular pain reliever ibuprofen, and a highly toxic cancer
medicine-to mimic the mixtures found in several Northern Italian rivers and
in wastewater. Individual component concentrations ranged from 10 to 1000
nanograms per liter. "The mixture is complex in terms of [what has] been used
[in laboratory tests] before, but it's nothing; it's simple in comparison to
what's been found in the environment," says Pomati.

To his surprise, Pomati observed that this mixture of drugs at environmental
levels inhibited the growth of human embryonic kidney cells. After 48 hours
of exposure, cell proliferation was reduced by 10-30% compared with controls.
However, no inhibition was observed when cells were exposed to only the toxic
cancer drug at environmental levels.

The results show that the growth inhibition is not due to the single most
cytotoxic compound alone. But that does not conclusively prove that
synergistic or additive effects exist between drugs in the mixture, cautions
Thomas Heberer of the Institute of Food Chemistry at the Technical University
of Berlin. To show that the individual drugs behave additively, Heberer
suggests that researchers should analyze the effects of compounds with a
common mode of action, such as antibiotics, alone and in various mixtures.
Nevertheless, many researchers speculate that such interactions are present,
although environmental impact assessments for new pharmaceuticals in the U.S.
and Europe are not required to take the possibility of mixture effects into
account.

Pomati and his colleagues used proteomic and genomic assays to determine the
mechanisms of growth inhibition. They found that the drug mixture stimulated
the expression of cell cycle regulation genes and certain proteins (kinases)
that signal cell stress. These responses often indicate a slower rate of cell
division and thus less cell proliferation.

According to Bent-Halling Sørensen, a professor of chemical toxicology at the
Danish University of Pharmaceutical Sciences, the proteomic and genomic
assays used by Pomati and his colleagues are becoming increasingly popular in
the field of environmental toxicology to study pharmaceuticals. "But you'll
have to remember that you have to translate something going on in an assay to
real life," he cautions, "and that's a big jump."

Another challenge lies in determining the bioavailability of the
pharmaceutical compounds, says Heberer, and this may depend on solubility and
other chemical properties. "So the question is: What really ends up in the
cells or close to these cells?"

Pomati concurs that extrapolating from cells to organisms is difficult, but
he believes that an understanding of the effects of pharmaceutical mixtures
in the environment is needed. "We have to demonstrate scientifically a
correlation between what we see in vitro and what we see in vivo. Organisms,
they are much more complex than cells, but that doesn't mean they're less
sensitive." 

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 at dep.state.fl.us
 
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