[Pharmwaste] Traces of Anxiety Drug May Affect Fish Behavior - another article about this research

[Jim Mullowney]

Good Morning Laurie.
Look what happens to fish that swim in water tainted by chemotherapy drugs!
The attached 2008 USGS Study found 62% of the fish in a cape cod pond had
cancer from a Genotoxic compound in the water. The DNA damage to the fish
matched the DNA damage to a fish injected with Cyclophosphamide, a baseline
carcinogen and the front line drug to battle breast, colon, lung and blood
cancers. A patient will get 4 grams of the drug and excrete 1 gram over the
first 24hrs, that is 1000 parts per million of a chemical designed to alter
human DNA. Cytotoxic drugs should not be collected at take back programs and
I am attaching the OSHA warnings, even hospitals have not drain disposed of
chemo in 20+ years.
If we accept that most of the drugs in the environment are from excretion
(PhRMA says 90% ) and we can accept that some drugs have no acceptable level
of exposure (OSHA) then we should be looking at controlling the source
starting with the worst ones first. There are 25 drugs that are excreted at
very dangerous levels and cause birth defects, cancer and other effects that
are irreversible even at single low level exposures (NIOSH). We put a car on
the moon we can collect pee in a cup.   I wanted to pass this to you to get
your opinion and please check out www.pharma-cycle.com 

-----Original Message-----
From: pharmwaste-bounces at lists.dep.state.fl.us
[mailto:pharmwaste-bounces at lists.dep.state.fl.us] On Behalf Of Tenace,
Laurie
Sent: Friday, February 15, 2013 8:22 AM
To: pharmwaste at lists.dep.state.fl.us
Subject: [Pharmwaste] Traces of Anxiety Drug May Affect Fish Behavior -
another article about this research


http://www.sfgate.com/news/science/article/Study-Fish-in-drug-tainted-water-
suffer-reaction-4278890.php

BOSTON (AP) - What happens to fish that swim in waters tainted by traces of
drugs that people take? When it's an anti-anxiety drug, they become hyper,
anti-social and aggressive, a study found. They even get the munchies.

It may sound funny, but it could threaten the fish population and upset the
delicate dynamics of the marine environment, scientists say.

The findings, published online Thursday in the journal Science, add to the
mounting evidence that minuscule amounts of medicines in rivers and streams
can alter the biology and behavior of fish and other marine animals.

"I think people are starting to understand that pharmaceuticals are
environmental contaminants," said Dana Kolpin, a researcher for the U.S.
Geological Survey who is familiar with the study.

Calling their results alarming, the Swedish researchers who did the study
suspect the little drugged fish could become easier targets for bigger fish
because they are more likely to venture alone into unfamiliar places.

"We know that in a predator-prey relation, increased boldness and activity
combined with decreased sociality ... means you're going to be somebody's
lunch quite soon," said Gregory Moller, a toxicologist at the University of
Idaho and Washington State University. "It removes the natural balance."

Researchers around the world have been taking a close look at the effects of
pharmaceuticals in extremely low concentrations, measured in parts per
billion. Such drugs have turned up in waterways in Europe, the U.S. and
elsewhere over the past decade.

They come mostly from humans and farm animals; the drugs pass through their
bodies in unmetabolized form. These drug traces are then piped to water
treatment plants, which are not designed to remove them from the cleaned
water that flows back into streams and rivers.

The Associated Press first reported in 2008 that the drinking water of at
least 51 million Americans carries low concentrations of many common drugs.
The findings were based on questionnaires sent to water utilities, which
reported the presence of antibiotics, sedatives, sex hormones and other
drugs.

The news reports led to congressional hearings and legislation, more water
testing and more public disclosure. To this day, though, there are no
mandatory U.S. limits on pharmaceuticals in waterways.

The research team at Sweden's Umea University used minute concentrations of
2 parts per billion of the anti-anxiety drug oxazepam, similar to
concentrations found in real waters. The drug belongs to a widely used class
of medicines known as benzodiazepines that includes Valium and Librium.

The team put young wild European perch into an aquarium, exposed them to
these highly diluted drugs and then carefully measured feeding, schooling,
movement and hiding behavior. They found that drug-exposed fish moved more,
fed more aggressively, hid less and tended to school less than unexposed
fish. On average, the drugged fish were more than twice as active as the
others, researcher Micael Jonsson said. The effects were more pronounced at
higher drug concentrations.

"Our first thought is, this is like a person diagnosed with ADHD," said
Jonsson, referring to attention deficit-hyperactivity disorder. "They become
asocial and more active than they should be."

Tomas Brodin, another member of the research team, called the drug's
environmental impact a global problem. "We find these concentrations or
close to them all over the world, and it's quite possible or even probable
that these behavioral effects are taking place as we speak," he said
Thursday in Boston at the annual meeting of the American Association for the
Advancement of Science.

Most previous research on trace drugs and marine life has focused on
biological changes, such as male fish that take on female characteristics.
However, a 2009 study found that tiny concentrations of antidepressants made
fathead minnows more vulnerable to predators.

It is not clear exactly how long-term drug exposure, beyond the seven days
in this study, would affect real fish in real rivers and streams. The
Swedish researchers argue that the drug-induced changes could jeopardize
populations of this sport and commercial fish, which lives in both fresh and
brackish water.

Water toxins specialist Anne McElroy of Stony Brook University in New York
agreed: "These lower chronic exposures that may alter things like animals'
mating behavior or its ability to catch food or its ability to avoid being
eaten - over time, that could really affect a population."

Another possibility, the researchers said, is that more aggressive feeding
by the perch on zooplankton could reduce the numbers of these tiny
creatures. Since zooplankton feed on algae, a drop in their numbers could
allow algae to grow unchecked. That, in turn, could choke other marine life.

The Swedish team said it is highly unlikely people would be harmed by eating
such drug-exposed fish. Jonsson said a person would have to eat 4 tons of
perch to consume the equivalent of a single pill.

Researchers said more work is needed to develop better ways of removing
drugs from water at treatment plants. They also said unused drugs should be
brought to take-back programs where they exist, instead of being flushed
down the toilet. And they called on pharmaceutical companies to work on
"greener" drugs that degrade more easily.

Sandoz, one of three companies approved to sell oxazepam in the U.S.,
"shares society's desire to protect the environment and takes steps to
minimize the environmental impact of its products over their life cycle,"
spokeswoman Julie Masow said in an emailed statement. She provided no
details.


-----Original Message-----
From: pharmwaste-bounces at lists.dep.state.fl.us
[mailto:pharmwaste-bounces at lists.dep.state.fl.us] On Behalf Of Volkman,
Jennifer (MPCA)
Sent: Thursday, February 14, 2013 8:07 PM
To: pharmwaste at lists.dep.state.fl.us
Subject: RE: [Pharmwaste] Traces of Anxiety Drug May Affect Fish Behavior,
Study Shows - NYT article

I listened to Charlotte Brody from the Bluegreen Alliance speak at a Green
Chemistry conference a couple of weeks ago. She talked about how the "dose
makes the poison" theory is no longer adequate to determine the potential
impacts of toxins. I've understood that for years, but she also stated that
certain toxins in minuscule doses are viewed by the body's endocrine system
as hormones, whereas in larger doses, the body views them as a toxin and
responds differently. I thought that was an interesting way to put that and
I see in this article, they are looking only at high dose responses vs.
ultra low doses and are nearly ignoring that lower doses might still cause
impacts. The accumulation aspect is not surprising but is interesting as
well. And of course I am trying to figure out whether it would be worthwhile
to soak my minnows in Oxazepam so they are more active and risky, to bring
in the big bite.

-----Original Message-----
From: pharmwaste-bounces at lists.dep.state.fl.us
[mailto:pharmwaste-bounces at lists.dep.state.fl.us] On Behalf Of Tenace,
Laurie
Sent: Thursday, February 14, 2013 2:15 PM
To: pharmwaste at lists.dep.state.fl.us
Subject: [Pharmwaste] Traces of Anxiety Drug May Affect Fish Behavior, Study
Shows - NYT article

http://www.nytimes.com/2013/02/15/science/traces-of-anxiety-drug-may-affect-
fish-behavior-study-shows.html?_r=0


Researchers in Sweden exposed wild European perch to water with different
concentrations of Oxazepam, a generic anti-anxiety medication that can show
up in waterways after being flushed, excreted or discarded.

Researchers reported that fish exposed to Oxazepam became less social, more
active and ate faster, behaviors they said could have long-term consequences
for aquatic ecosystems.

Scientists who study pharmaceuticals in waterways said the research was
intriguing because it examined the potential effect on animals of a specific
medication designed to affect human behavior.

"It seems to be a solid study with an environmentally relevant species,"
said Donald Tillitt, an environmental toxicologist with the United States
Geological Survey who was not involved in the study. He said it made sense
that a medication that binds with a certain brain receptor in people could
act similarly in fish, and the measures of behavior - activity, sociability,
boldness and feeding rate - "are all important ones that we like to look at
when we're trying to see the environmental effects of pharmaceuticals."

Still, because even the lowest concentration of Oxazepam in the study was
higher than that found in the Swedish waterway researchers tested, "the
relevance of their study to the real world is unclear," the Environmental
Protection Agency said in written answers to questions.

The agency said that while "most pharmaceuticals do not seem to pose known
risks to humans, animals or the rest of the ecosystem" at the levels they
occur in the environment, there are some medications "for which some
researchers have noted physiological effects in fish exposed to levels close
to those occasionally reached in the environment. These include some
ingredients used for contraception, hypertension and mood disorders."

The agency said how often this occurs and the possible environmental
repercussions are unknown.

The study joins a small but growing body of research exploring the possible
environmental impact of chemicals in pharmaceuticals, cosmetics and other
products. Many of these chemicals are not removed by wastewater treatment
plants, which were designed to remove bacteria and nutrients, experts said.

The topic is difficult to study partly because concentrations of chemicals
in waterways can vary with season, hour and distance from treatment plants,
and other medications in water may influence a chemical's effects.

The United States Geological Survey has found "intersex fish," or male fish
that develop female sexual characteristics, in the Potomac River and its
tributaries, raising questions about whether hormone residues might be
responsible. A study in the journal Environmental Science and Technology
found antidepressants like Prozac and Zoloft in the brains of fish collected
downstream from wastewater discharge in Colorado and Iowa. But some
antidepressants that were more common in those waterways, including Zyban
and Citalopram, were not found as frequently in the fish.

In the Swedish study, researchers first tested perch in the
wastewater-treated Fyris River, near the city of Uppsala, and found their
muscle tissue contained six times the river's concentration of Oxazepam,
said Tomas Brodin, the lead author and an assistant professor of ecology at
Umea University.

Researchers then took baby fish hatched from the roe of wild perch in what
they considered a drug-free waterway, and divided them into three groups of
25. One group had no exposure to Oxazepam; the other two were placed in
water with what researchers called a low concentration, at three times
higher than the River Fyris, or an extremely high concentration, at 1,500
times higher.

The more Oxazepam they ingested the more active the fish were, measured by
the number of swimming motions in a 10-minute period. They were also less
social, spending less time near a section of the tank with other fish and
more time near an empty compartment. And they were quicker to grab and eat
zooplankton. At the highest Oxazepam concentration, fish were also bolder,
measured by how long it took them to leave a box in the tank and explore new
territory.

"Basically, no one left the box before they were subjected to the drug,"
said Dr. Brodin, who said he saw the difference when he entered the room
each day. The non-exposed fish "were hiding basically," while the others
"were out there, greeting me. They were totally different fish."

In a statement, Matthew Bennett, senior vice president of the Pharmaceutical
Research and Manufacturers of America, said the study yielded "somewhat
expected results" because of its higher-than-natural concentrations. He said
the behavioral changes were small, and the study methods contradicted
"widely accepted protocols that determine how the low levels of Oxazepam
found in the environment accumulate in fish. The environmental relevance and
potential for long-term impact from this drug, which has been in use for
decades are therefore debatable."

Joel A. Tickner, an environmental scientist at the University of
Massachusetts, Lowell, who was not involved in the research, said he
considered the study significant. "These effects may be very subtle," he
said, but "what they're finding is it's biologically relevant."

Dr. Brodin, the lead author of the study, said the implications were unclear
for perch, which might benefit from Oxazepam exposure by becoming more
efficient eaters or be disadvantaged because enhanced risk-taking behavior
might increase their vulnerability to predators. Zooplankton, algae and
other organisms could also be affected by changes in fish behavior, he said.

Dr. Tillett, the toxicologist with the Geological Survey, said, "We're smart
enough and we should be able to design chemicals that fulfill these same
sorts of functions but with less stress on the environment."


Laurie Tenace
Environmental Specialist III
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
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