- Chemists at an agricultural research
laboratory run by the Swiss government were screening lake water for pesticide
contamination when they ran across a puzzling result. Their instruments
turned up a compound that resembled mecoprop, an herbicide they had been
looking for, but it wasn't a perfect match.
- Suspecting that they might have found
the pesticide in an early stage of degradation, Hans-Rudolf Buser and Markus
D. Müller probed further. To their surprise, the pollutant turned
out to be clofibric acid, a widely used cholesterol-lowering drug.
- Immediately, the pair began scouting
for the drug elsewhere -- and they found it everywhere, from rural mountain
lakes to rivers flowing through densely populated areas. Concentrations,
ranging from 1 to 100 nanograms per liter of water, seemed to correlate
with how densely a region was inhabited. While barely detectable, these
concentrations resemble those of other, more conventional pollutants found
in the environment, Buser notes, such as a persistent, toxic ingredient
of the pesticide lindane (SN: 3/15/97, p. 157).
- The ubiquity of clofibric acid, which
is not even manufactured in Switzerland, argued against the possibility
that the contamination stems from some industrial accident or spill, Buser
says. The only reasonable explanation, he and Müller conclude in the
Jan. 1 Environmental Science & Technology, is that it comes from human
wastes. Sewage treatment plants have not been designed to remove excreted
drugs before releasing their effluent into public waterways.
- Though the body tends to break down any
medicine it uses, how effectively it does so can vary widely -- by individual
and by drug. As a result, in some cases, 50 to 90 percent of an administered
drug may be excreted from the body in its original or its biologically
active form. In other cases, partially degraded drugs are converted back
into their active form through chemical reactions with the environment.
- Seven years earlier, environmental chemists
Thomas Heberer and Hans-Jürgen Stan of the Technical University of
Berlin had stumbled upon clofibric acid while looking for agricultural
chemicals in groundwater beneath a German sewage treatment farm. Heberer
suspects that he and Stan would have missed the drug if it hadn't resembled
a common pesticide. The drug's structural similarity, he says, "proved
the key to its detection."
- Like the Swiss team, the Berlin scientists
went on to find clofibric acid throughout local waters. It laced some groundwater
at concentrations of up to 4 milligrams per liter, or 4 parts per billion
(ppb), they will report in an upcoming issue of the International Journal
of Environmental Analytical Chemistry. It also turned up in all the Berlin
tap water they sampled -- at up to 0.2 ppb.
- When it comes to waterborne drugs, however,
clofibric acid is just the tip of the iceberg. Heberer and Stan are part
of a Berlin research team that has found drugs for regulating concentrations
of lipids in the blood (such as phenazone and fenofibrate) and analgesics
(including ibuprofen and diclofenac) in groundwater beneath a sewage treatment
plant. This aquifer serves as a source of drinking water. Other researchers
have detected chemotherapy drugs, antibiotics, and hormones in bodies of
water that supply drinking water.
- What do low concentrations of these drugs
in water mean? asks ecotoxicologist Bent Halling-Sørensen of the
Royal Danish School of Pharmacy in Copenhagen. Do they pose a health risk
to people? Can they harm wildlife or substantially alter aquatic ecosystems?
Do they foster the buildup of resistance to antibiotics?
- For now, there are no answers, he and
his colleagues conclude in the January (No. 2) Chemosphere. After reviewing
more than 100 published reports on drug residues in the environment, they
found "practically zero" data for gauging the potential toxicity
of chronic exposures to low doses of these compounds in the environment.
- Most countries have regulatory agencies
explicitly charged with protecting the environment from pesticides and
other potentially toxic industrial chemicals.
- Drugs, however, have come to be regulated
by health departments, which possess little expertise in protecting natural
ecosystems and water supplies. Moreover, they tend not to look at pharmaceuticals
as potential pollutants -- even though up to 90 percent of a delivered
drug may leave the body in urine and feces.
- One reason for medicines' low visibility
in environmental regulations is their low concentrations in water. Until
recently, most drugs in public water supplies would have been undetectable.
- Regulators have attempted to cope with
this problem by asking manufacturers to model a new drug's projected concentration
in public water supplies, based on what was known about company projections
for how much of the compound might be sold, the quantities of lake and
stream water into which the excreted drug would be flushed, and laboratory
information on the rate at which it would break down in the environment.
They were also asked to predict its accumulation in wildlife.
- In the United States, an environmental
assessment containing such estimates would be submitted to the Food and
Drug Administration as part of the approval process for a new drug. If
such an assessment suggested that worrisome levels of a drug might build
up, a manufacturer would have to prepare a more detailed investigation.
Such an environmental impact statement might even explore possible mitigation
measures, explains Daniel C. Kearns of FDA in Rockville, Md.
- So seldom did an environmental assessment
for a new drug suggest a hazard, however, that the FDA decided last July
to reduce a manufacturer's environmental reporting requirements. The agency
concluded that excreted drugs "are probably not having a significant
environmental effect," Kearns says. "So unless modeling data
suggest a drug's concentrations would reach 1 ppb, a manufacturer no longer
must submit an environmental assessment.
- "We've never seen a situation where
we believe you would have an actual impact upon the environment if [drug]
concentrations were under that," he told Science News.
- Though modeling provided a useful surrogate
for water monitoring when laboratory analyses were too crude to detect
low drug concentrations in the environment, chemists today routinely detect
parts per trillion (ppt) of many waterborne pollutants.
- When asked whether FDA requires any monitoring
of water supplies to see whether concentrations in the real world match
the predictions of drug manufacturers' models, Kearns said no.
- If they had, many German chemists now
believe, regulators might have received a rude awakening -- as Thomas A.
- A chemist with the municipal water research
laboratory in Wiesbaden, Ternes realized that tons of medicines are prescribed
each year in Germany, "but nobody knows what happens to those compounds
after they are excreted." So a few years ago he launched a water-monitoring
project to look for drugs in sewage, treated water, and rivers.
- He expected to find a few medicinal compounds.
Instead, he detected 30 of the 60 common pharmaceuticals for which he tested.
These included lipid-lowering drugs, antibiotics, analgesics, antiseptics,
and beta-blocker heart drugs. He has even found residues of drugs to control
epilepsy and ones that serve as contrast agents for diagnostic X rays.
A report of his findings will appear later this year in Water Research.
- Ternes detected parts-per-billion concentrations
of these drugs in both raw sewage and the water leaving treatment plants.
"We also found these compounds in nearly all streams and rivers in
Germany," he says. Though concentrations in streams usually fall in
the parts-per-trillion range, he notes that for some compounds "you
can have maximum concentrations of up to 3 [ppb]."
- The highest concentrations tended to
show up in the smallest rivers, where 50 percent of the water could be
sewage treatment effluent. Residues of up to 10 different drugs have been
found in such water at concentrations totaling 6 ppb.
- Ternes notes that finding these drugs
"is very hard work." For instance, chemists usually identify
a compound by comparing it against a standard sample of that compound.
These standards often are not available for sale, he finds.
- Adding to the problem, Heberer observes,
is that almost all excreted drugs dissolve easily in water. Because conventional
methods of separation take advantage of differences in the effectiveness
of several solvents, it is difficult to segregate the drugs for analysis.
That's a problem Shane Snyder at Michigan State University in East Lansing
has been wrestling with in his study of estrogens in sewage effluent.
- While analyzing Las Vegas wastewater
flowing into Lake Mead, Snyder found that "all of the estrogenicity
was coming out of the very water-soluble fraction." To isolate the
chemicals responsible, he had to repeat the separation procedure 30 times
or more. Though estradiol, the primary natural female sex hormone, appears
to be the major estrogenic compound in this water, there is evidence that
a synthetic hormone in birth control pills may also be a contributor. Further
investigation of that possibility is now under way.
- "These findings are not all that
surprising," observes James F. Pendergast, acting director of the
Environmental Protection Agency division that regulates what comes out
of sewage treatment plants. For quite a while, he notes, water quality
engineers have recognized that one of the highest-volume contaminants emerging
in effluent -- especially early in the morning -- is caffeine, a drug excreted
by all those people who down a cup or two of Java to jolt their bodies
- Although he was unfamiliar with the new
European studies documenting drugs in water, Pendergast says that he has
no reason to doubt their findings or the possibility that they might herald
what could be found in U.S. waters, if anyone were to look.
- He's also not surprised that European
chemists have stumbled onto the issue before U.S. scientists. A number
of environmental issues -- from methyl mercury buildups in acidified lakes
to reproductive risks from hormone-mimicking pollutants -- became hot research
topics in Europe before U.S. researchers jumped on the bandwagon, he says.
- The issue of drugs in water, he concludes,
"is certainly an area where we could use a lot more science."
The critical issue is whether existing concentrations pose any hazard to
wildlife or to people. To date, he notes, "information on hazards
at the nanogram level just hasn't been developed."
- A few laboratories stand poised to try.
Snyder's assays, for instance, indicate that estradiol in water can reach
20 ppt -- a concentration that can cause some male fish to produce an egg-making
protein normally seen only in reproductive females. In upcoming experiments
in Lake Mead, he plans to cage fish within a plume of effluent from an
upstream sewage treatment plant.
- Using a bacterial test that gauges a
pollutant's potential to damage DNA, Andreas Hartmann of the Swiss Federal
Institute of Technology in Zurich has been studying effluent from hospitals
and municipal wastewater treatment plants. In the March Environmental Toxicology
and Chemistry, he reports finding fluoroquinolones, a class of broad-spectrum
antibiotics, to be the leading source of a hospital wastewater's toxicity
- "We're finding 0.5 microgram per
liter of fluoroquinolone antibiotics in sewage treatment plant water,"
Hartmann told Science News. Tests have tentatively identified the drug
as ciprofloxacin. Once the antibiotic is more firmly identified, he plans
to study "whether it -- alone or in combination with other antibiotics
-- has an influence on the developing resistance to these compounds that
we're finding in pathogenic organisms in the environment."
- "If [he's] finding fluoroquinolone
antibiotics at that level in water and they're not breaking down, that
would be a problem," says Stuart Levy, who directs the Center for
Adaptation Genetics and Drug Resistance at Tufts University in Boston.
Parts-per-trillion concentrations of these drugs can affect Escherichia
coli and other bacteria, he notes. The 1,000 times higher concentrations
reported in German wastewater suggest to Levy that "these antibiotics
may be present at levels of consequence to bacteria -- levels that could
not only alter the ecology of the environment but also give rise to antibiotic
- Halling-Sørensen is also studying
waterborne antibiotics, though his focus is their potential toxicity to
algae, crustaceans, and other aquatic residents. By quantifying the potential
ecological effects of individual compounds, he says, "we may get information
that's useful for decision making.
- "For instance, if we have five medicinal
compounds that can treat the same disease, we might now identify which
is most friendly to the ecosystem -- and choose to use that one."
- Buser, H., M.D. Muller, and N. Theobald.
1998. Occurrence of the
- pharmaceutical drug clofibric acid and
- mecoprop in various Swiss lakes
and in the North Sea. Environmental
- Science and Technology 32(Jan. 1):188.
- Halling-Serensen, B., et al. 1998.
Occurrence, fate and effects of
- pharmaceutical substances in the environmenta
- review. Chemosphere 36(January):357.
- Hartmann, A. In Press. Identification
- antibiotics as the main source of umuC
genotoxicity in native
- hospital. Environmental Toxicology
and Chemistry 17:3.
- Hartmann, A., et al. 1997. Determination
of the fluoroquinolone
- antibiotic ciprofloxacin in hospital
and municipal water.
- Society of Environmental Toxicology
and Chemistry. San Francisco.
- Heberer, T. 1997. Determination
of clofibric acid and
- N-(phenylsulfonyl)-sarcosine in sewage,
river and drinking water.
- Journal of Environmental Analytical
- Heberer, T. et al. 1997. Detection
of drugs and drug metabolites in
- ground water samples of a drinking water
- plant. Fresenius Environmental Bulletin
- Snyder, S., et al. 1997. Toxicant
identification and evaluation
- (TIE) of endocrine disrupters in aqueous
- Society of Environmental Toxicology
and Chemistry. San Francisco.
- Steger-Hartmann, T., K. Kummerer,
and A. Hartmann. 1997. Biological
- degradation of cyclophosphamide and its
- occurrence in sewage water. Ecotoxicology
and Environmental Safety
- Ternes, T.A. In press. Occurrence
of drugs in German sewage
- treatment plants and rivers. Water Research.
- Further Readings:
- 1997. National Environmental Policy
Act: Revision of policies and
- procedures. Federal Register 62(July
- Burhenne, J., et al. 1997. Chemotherapeutic
- photoproducts and half-lives. Environmental
- Pollution Research 4:10.
- 1997. Chemotherapeutic agents: Isolation
- elucidation of polar photometabolites.
- Science and Pollution Research 4:61.
- Knepper, T.P., and K. Haberer. Auftreten
von phenylsulfonamiden in
- trinkwässern(Occurrence of
phenylsulfonamides in sewage,
- surfaceand tap waters). Vom Wasser 86:263.
- in English).
- Renner, R. 1998. Human estrogens
linked to endocrine disruption.
- Environmental News 32(Jan. 1):8.
- Sallustio, B.C., et al. Genotoxicity
of acyl metabolites formed
- from clofibric acid and gemfibrozil:
A novel role for
- Phase-II mediated bioactivation
in the hepatocarcinogenicity of the
- parent aglycones? Toxicology and Applies
- Pharmacology 147(December):459.
- Schlett, C., und B. Pfeifer. 1996.
Bestimmung von steroidhormonen
- in trinkund oberflächenwässern.
- steroidal hormones in drinking and
surface water samples.) Vom
- Wasser 87:237. (Abstract in English).
- Stan, H.J., and T. Heberer. Pharmaceuticals
in the aquatic
- environment. Analusis 25:20.
- Stumpf, M., et al. 1996. Nachweis
von arneimittelruckstänlagen und
- flieb gewässern. (Determination
- in sewage plants and river water).
Vom Wasser 86:291.
- Bent Halling-Serensen
- Royal Danish School of Pharmacy
- Institute of Analytical and Pharmaceutical
- Section of Environmental Chemistry
- Universitetsparken 2
- DK 2100 Copenhagen Ø
- Andreas Hartmann
- Swiss Federal Institute of Technology
- Department of Environmental Sciences
- Institute for Hygiene and Applied
- Clausiusstr. 25
- CH-8092 Zuerich
- Thomas Heberer
- Technical University of Berlin
- Institute of Food Chemistry
- Gustav-Meyer-Alleee 25
- D-13355 Berlin
- Daniel C. Kearns
- U.S. Food and Drug Administration
- Center for Biologics Evaluation
and Research (HFM-208)
- 1401 Rockville Pike
- Rockville, MD 20852
- Stuart Levy
- Tufts medical School
- Center for Adaptation Genetics and
- 136 Harrison Avenue
- Boston, MA 02111
- James F. Pendergast
- Environmental Protection Agency
- NPDES Permit Division
- MC 4203
- 402 M Street, S.W.
- Washington, DC 20460
- Shane Snyder
- Michigan State University
- 201 Pesticide Research Center
- East Lansing, MI 48824
- Thomas Steger-Hartmann
- Experimental Toxicology
- Scherling AG
- D-13342 Berlin
- Thomas Ternes
- ESWE-Institute for Water Research
and Water Technology
- Soehnleinstr. 158
- D-65201 Wiesbaden