WHAT ARE OUR PHARMACEUTICALS DOING TO THE ENVIRONMENT? - American Chemical Society

[Guest guest]

Here's our latest dilemma:

What if the teenage boys who are developing lactating breasts from Risperdal eat

estrogen-laden fish?!?!?!?!?

Terry

http://www.precaution.org/lib/08/prn_pharmaceuticals_in_water.080225.htm

Chemical & Engineering News (pg. 13), February 25 2008

WHAT ARE OUR PHARMACEUTICALS DOING TO THE ENVIRONMENT?

['s introduction: People and animals excrete pharmaceuticals and their

metabolites, which then find their way into the environment through a variety of

routes -- treated wastewater, agricultural runoff, and biosolids and manure that

are used as fertilizers.]

By Bethany Halford

No one ever planned for fish to take birth control pills. But they are. As

treated wastewater flows into rivers and streams every day, fish all over the

world get a tiny dose of 17a-ethinylestradiol, a synthetic steroidal estrogen

that's used in birth control pills. They also get a little sip of the

anticonvulsant carbamazepine, a nip of the antidepressant fluoxetine, and a

taste of hundreds of other drugs that we take to make our lives better.

Every drug begins its life as a promise -- a promise to fight disease or improve

our quality of life. It wends its way through the discovery process and clinical

trials until it ends up in our bodies, ready to do its job.

But that's not the end of the story. A drug doesn't simply disappear once it has

served its purpose. People and animals excrete pharmaceuticals and their

metabolites, which then find their way into the environment through a variety of

routes -- treated wastewater, agricultural runoff, and biosolids and manure that

are used as fertilizers. Pharmaceuticals also enter the environment when people

dispose of medications by flushing them down the toilet or pouring them down the

drain.

========================================================

What to do with your unused pharmaceuticals.

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Concentration-wise, pharmaceuticals represent just a small fraction of the

thousands of man-made chemicals in the environment, including everything from

pesticides to personal care products. Even though medications have been in the

environment for as long as people have been taking them, it's only through the

advent of advanced analytical instrumentation and techniques that scientists

have been able to detect them in the wild.

The small concentrations, however, belie the potentially powerful effects of

these compounds. Pharmaceuticals are specifically designed to elicit a

biological response at very low levels, and scientists are increasingly becoming

aware of how medications let loose on the environment may have effects no one

ever anticipated.

By far, the most dramatic example of this kind of pharmaceutical pollution has

been the effect of estrogenic compounds on fish. In the 1990s, scientists

working in the U.K. noted that male fish living downstream from wastewater

treatment plants were becoming feminized. They were making proteins associated

with egg production in female fish, and they were developing early-stage eggs in

their testes. Feminized male fish have now been observed in rivers and streams

in the U.S. and Europe.

Research led by Sumpter, an ecotoxicologist at England's Brunel University,

linked the feminizing phenomenon to the presence of estrogenic compounds, such

as the synthetic birth control compound 17a-ethinylestradiol and the natural

hormone 17beta-estradiol, in the water (Environ. Sci. Technol. 1998, 32, 1549).

Municipal wastewater treatment plants don't completely break down these

estrogenic compounds or their metabolites. For example, 17a-ethinylestradiol is

excreted in the form of glucuronide and sulfate conjugates. Bacteria in the

wastewater treatment process cleave these conjugate groups, regenerating the

original estrogenic compound.

" It doesn't take a lot of estrogen to feminize male fish, " says A. Kidd, a

biology professor at the Canadian Rivers Institute, University of New Brunswick.

" If you can measure the estrogen in the water, then that's enough to cause an

effect, and we can measure it at very low parts-per-trillion concentrations. "

Kidd recently spearheaded a research project to study the overall impact of

estrogenic compounds on fish (Proc. Natl. Acad. Sci. USA 2007, 104, 8897). " No

one knew what feminization meant for the fish population, " Kidd explains. " Can

feminized males still successfully reproduce, or is there going to be an impact

on the number of fish in the rivers? That's the big question we set out to

address. "

FOR THREE SUMMERS, Kidd and her colleagues spiked a lake in Canada's

Experimental Lakes Area with 17a-ethinylestradiol at a concentration of 5 ppt --

a concentration that has been measured in municipal wastewaters and in river

waters downstream of discharges. During the autumn that followed the first

addition of the estrogenic compound, the researchers observed delayed sperm cell

development in male fathead minnows -- the freshwater equivalent of a canary in

a coal mine. A year later, the male fathead minnows were producing eggs and had

largely stopped reproducing. The minnow population began to plummet. The decline

continued for an additional three years until the fish had all but disappeared

from the lake.

The fathead minnow wasn't the only fish to feel the effects of the trace amounts

of birth control. The population of lake trout, which feed on smaller fish, fell

by about 30%. " The numbers of lake trout dropped not because of direct exposure

to the estrogens but because they lost their food supply, " Kidd says.

But Kidd's story is not all doom and gloom. In 2006, three years after her team

stopped adding 17a-ethinylestradiol to the lake, the fathead minnow population

rebounded. " So given enough time, once you remove the estrogens from a system,

the fish can recover to their original population size, " Kidd notes.

Although estrogenic compounds may have the most dramatic effect on fish, they

aren't the only pharmaceuticals that have been implicated in the pollution of

aquatic environments. Laboratory studies have shown that the antidepressant

fluoxetine, or Prozac, can slow the development of fish and frogs. The

anticonvulsant carbamazepine affects the emergence of mosquito-like insects that

are a popular food source for certain fish.

" The challenge is that we don't have a good understanding of " a lot of drugs

that are being used, Kidd says. " We've looked at only a handful of the drugs

that are actually used and discharged into our waters. There are just a lot of

unknowns in this field right now. "

And it's not just aquatic organisms that are feeling the effects of

pharmaceutical pollution. One study traced massive die-offs of vultures in Asia

to the veterinary use of diclofenac, a nonsteroidal, anti-inflammatory (Nature

2004, 427, 630).

Diclofenac is frequently used to treat domestic livestock in India and Pakistan.

When these animals die from disease or injury, they're typically left for

scavengers. An international team of scientists, led by J. Oaks of

Washington State University, found that the vultures were consuming these

carcasses and dying from renal failure and visceral gout caused by diclofenac

poisoning.

Scientists also worry that the massive amounts of antibiotics used to treat

livestock may be creating antibiotic-resistant microbes. " There's a whole other

source of pharmaceutical pollution that really needs attention, and that's

livestock use, which generates an estimated 500 million tons of waste each

year, " says Dana W. Kolpin, a research hydrologist at U.S. Geological Survey

(USGS) who studies emerging contaminants in the environment.

Kolpin points out that livestock manure is full of antibiotics, synthetic and

biogenic hormones, and other veterinary medicines. Farmers use sludge generated

by sewage treatment plants as a fertilizer and a source of nutrients for crops,

but this material also contains excreted medications.

SCIENTISTS KNOW that these pharmaceuticals can travel into the environment as

agricultural runoff and soil contaminants. A new report from chemistry professor

Chad A. Kinney of Colorado State University, Pueblo, shows that earthworms

living in the contaminated soil can take up some of these pharmaceuticals,

notably the antibiotic trimethoprim, albeit in small amounts (Environ. Sci.

Technol., DOI: 10.1021/es702304c). " It shows there is uptake into earthworms

that leads to a potential pathway up the food chain, as earthworms are a major

food source for many higher organisms, " says Kolpin, who was a coauthor of the

report. Studies have also shown that pharmaceuticals can be taken up into crop

plants (J. Agric. Food Chem. 2006, 54, 2288).

Researchers continue to suss out the subtle effects of pharmaceuticals on the

environment, such as antibiotic resistance and changes in feeding and mating

behaviors. But getting a handle on the whole problem is a huge task. Not only do

researchers need to consider the parent compounds in their analyses, but they

also have to look at metabolites and at the transformation products that are

formed either during treatment or from natural processes taking place in the

environment, such as microbial degradation and photolysis.

" If you just look at the parent compound, that's only giving you a piece of the

story, " Kolpin explains. " Each compound can break down and form new

environmental contaminants, which can become much more mobile and much more

persistent. "

" Sometimes there are cases for which the biodegradation product is more toxic

than the parent compound, " adds Aga, an analytical chemist at State

University of New York, Buffalo, who is developing tools to detect trace levels

of pharmaceuticals.

Scientists also have to keep in mind that pharmaceuticals aren't isolated in the

environment, Kolpin notes. They could be acting in concert with a surfactant,

another pharmaceutical, or some other environmental contaminant.

The Food & Drug Administration requires pharmaceuticals to undergo an

environmental risk assessment before they can go on the market. These tests are

performed on both terrestrial and aquatic organisms, but they're usually

short-term tests that measure how much of a compound is required to kill an

organism outright or stunt its growth within a matter of days.

" If we're going to identify the compounds that are going to be problematic, we

need to be looking for the right things, " says , an environmental

science professor at Baylor University. For example, he explains, it takes a lot

of 17a-ethinylestradiol to kill an aquatic organism, so by current testing

standards, the compound would appear to have a very low potential risk. But

feminization of male fish -- something those short-term tests would have never

detected -- occurs at very low concentrations of the drug.

THE BIG QUESTION is whether pharmaceutical pollution has any impact on human

health. While trace amounts of pharmaceuticals do find their way into drinking

water, studies indicate that the concentrations are far too small to elicit any

appreciable effect.

Fetal exposure to certain pharmaceuticals is also a cause for concern. An

extreme example would be exposure to thalidomide or to a chemotherapeutic drug,

says Christian G. Daughton, chief of the environmental chemistry branch at the

Environmental Protection Agency's National Exposure Research Laboratory. He

adds, however, that " the doses that a fetus would get from its mother ingesting

several liters of water a day are still orders of magnitude below the dosages

that are known to cause effects. "

Daughton says that toxicologists are now trying to understand the effects of

continual sustained exposure to multiple chemicals, each present at a very low

level. " It could be that the chemical stress that's put on any organism is the

result of minute stresses of a multitude of chemicals, " whether they're

synthetic or naturally occurring compounds, he says.

Francesco Pomati, a toxicologist at Australia's University of New South Wales,

and colleagues at Italy's University of Insubria recently discovered that a

low-concentration mixture of 13 drugs -- including a chemotherapeutic agent and

several antibiotics -- can inhibit the growth of human embryonic kidney cells in

vitro (Environ. Sci. Technol. 2006, 40, 2442). It's important to note, however,

that the concentrations used were those found in the environment, not in

drinking water.

" Studies conducted to date suggest that it is highly unlikely that the

quantities of pharmaceuticals detected in the environment would be harmful to

human health, " says Ken , senior vice president with Pharmaceutical

Research & Manufacturers of America.

" I think it's unambiguous that the trace pharmaceuticals we're seeing in

drinking water have no human health problems so far, " adds Shane Snyder, an

environmental toxicologist at the Southern Nevada Water Authority. A few months

ago, Snyder published an analysis of water from 20 drinking water utilities

across the U.S. These utilities were treating water known to contain wastewater

that had come from a sewage treatment plant upstream.

Notably, Snyder's team did not detect any of the estrogenic compounds that have

been implicated in the feminization of fish in either the source water or the

treated drinking water. They did find that drinking water from at least half of

the treatment facilities contained ibuprofen, carbamazepine, the antiepileptic

dilantin, and the antianxiety drug meprobamate, but each occurred in extremely

low concentrations -- in the parts-per-trillion range.

" The treatment processes we have are highly effective, " Snyder concludes. He

points out that we're seeing more pharmaceuticals in our environment because

we're getting better at detecting them, not necessarily because there are more

of them. It's therefore important, he says, to develop toxicologically based

limits for pharmaceuticals in our water. " If we ignore concentration and say

presence or absence is our litmus test, then there will be no end to that, "

Snyder says. " Detection does not infer health risk and nondetection does not

ensure safety. "

Snyder's study also assessed the removal of pharmaceuticals from drinking water,

using both conventional and advanced drinking water treatment processes.

Conventional treatments, such as coagulation, flocculation, and filtration, were

basically ineffective. Chlorination proved to be better, removing about half of

the compounds considered in the study. Advanced treatments, such as ozonation,

activated carbon, and reverse osmosis and nanofiltration membranes, worked well,

but these methods are expensive, and they're generally used to treat drinking

water, not wastewater.

" YOU HAVE TO keep in mind that sewage treatment plants were originally designed

a long time ago to improve the aesthetic quality of treated sewage and to reduce

the incidence of disease -- to reduce odor and make the water look better and

get rid of bacteria and viruses, " EPA's Daughton says. " They were never

engineered to remove synthetic substances. "

Whether or not sewage treatment plants should be equipped to remove

pharmaceuticals is a matter of some controversy. " There's this huge risk-benefit

equation that's very difficult to address, " Daughton explains.

" I think for a lot of drugs out there, we are probably more concerned than we

should be, " says Alistair Boxall, an environmental chemist at the University of

York, in England. " I think there are examples of substances that perhaps we do

need to look at a bit further, but I'm not convinced we should be putting

advanced treatment mechanisms on every sewage treatment plant just to get rid of

pharmaceuticals. "

Snyder agrees. " I would be very cautious about building energy- intensive

wastewater treatment plants, " he tells C & EN.

" With regard to pharmaceuticals in the environment, I do believe that we have

the treatment technologies available to address these problems, " says G.

Love, a professor of civil and environmental engineering at Michigan University.

" The challenge comes in improving the engineering implementation of the

technologies " to make them more cost-effective, she adds.

Even though pharmaceutical pollution is a problem we are equipped to deal with,

the solution may not be so simple if the contaminants are causing antibiotic

resistance, Love says. " We do not necessarily have the technology to design

antibiotics that are not vulnerable to generating antibiotic-resistant

characteristics in microbes. And if pollution is an inducer of antibiotic

resistance, then we have a larger problem on our hands than we realize. "

Scientists working in this area agree that more research needs to be done on all

aspects of pharmaceuticals' effects in the environment. " We need to determine

which compounds or sets of compounds are the worst players, and then we need to

make the decision whether these things need to be removed before they get into

the environment, " USGS's Kolpin says. " There's more information needed before

any sort of policy or regulatory decision can be made. Otherwise, I'm afraid it

will be ineffective or unnecessary. "

Copyright 2008 American Chemical Society

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