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Pharmaceuticals In Our Water Supplies

Are “Drugged Waters” a Water Quality Threat?
Arizona Water Resource

Developed to promote human health and well being, certain pharmaceuticals are now attracting attention as a potentially new class of water pollutants. Such drugs as antibiotics, anti-depressants, birth control pills, seizure medication, cancer treatments, pain killers, tranquilizers and cholesterol-lowering compounds have been detected in varied water sources.

Where do they come from? Pharmaceutical industries, hospitals and other medical facilities are obvious sources, but households also contribute a significant share. People often dispose of unused medicines by flushing them down toilets, and human excreta can contain varied incompletely metabolized medicines. These drugs can pass intact through conventional sewage treatment facilities, into waterways, lakes and even aquifers. Further, discarded pharmaceuticals often end up at dumps and land fills, posing a threat to underlying groundwater.

Farm animals also are a source of pharmaceuticals entering the environment, through their ingestion of hormones, antibiotics and veterinary medicines. (About 40 percent of U.S.-produced antibiotics are fed to livestock as growth enhancers.) Manure containing traces of such pharmaceuticals is spread on land and can then wash off into surface water and even percolate into groundwater.

Along with pharmaceuticals, personal care products also are showing up in water. Generally these chemicals are the active ingredients or preservatives in cosmetics, toiletries or fragrances. For example, nitro musks, used as a fragrance in many cosmetics, detergents, toiletries and other personal care products, have attracted concern because of their persistence and possible adverse environmental impacts. Some countries have taken action to ban nitro musks. Also, sun screen agents have been detected in lakes and fish.

Researchers Christian G. Daughton and Thomas A. Ternes reported in the December issue of “Environmental Health Perspectives” that the amount of pharmaceuticals and personal care products entering the environment annually is about equal to the amount of pesticides used each year.

Concern about the water quality impacts of these chemicals first gained prominence in Europe, where for over a decade scientists have been checking lakes, streams, and groundwater for pharmaceutical contamination. American officials and scientists are taking note, with two recent U.S. professional organizations — the National Ground Water Associations and the American Chemical Society — addressing the issue at their annual meetings this summer.

The issue emerged in Europe about ten years ago, when German environmental scientists found clofibric acid, a cholesterol-lowering drug, in groundwater beneath a German water treatment plant. They later found clofibric acid throughout local waters, and a further search found phenazone and fenofibrate, drugs used to regulate concentrations of lipids in the blood, and analgesics such as ibuprofen and diclofenac in groundwater under a sewage plant. Meanwhile other European researchers discovered chemotherapy drugs, antibiotics and hormones in drinking water sources.

In the United States, the issue might have attracted earlier notice if officials had followed up on observations made 20 years ago. At that time, EPA scientists found that sludge from a U.S. sewage-treatment plant contained excreted aspirin, caffeine and nicotine. At the time, no significance was attached to the findings.

In Phoenix about this time another event occurred that also might have alerted officials that pharmaceuticals could pose a water quality threat. Herman Bouwer of the U.S. Agricultural Research Service in Phoenix recalls that clofibric acid was found in groundwater below infiltration basins that were artificially recharging groundwater with sewage effluent. Bouwer says more attention should have been paid to the finding; if clofibric acid could pass through a sewage treatment plant and percolate into the groundwater so also could many other drugs.

Europeans, however, took the lead in researching the issue. In the mid-1990s, Thomas A. Ternes, a chemist in Wiesbaden, Germany, investigated what happens to prescribed medicines after they are excreted. Ternes knew that many such drugs are prescribed, and that little was known of the environmental effects of these compounds after they are excreted. He researched the presence of drugs in sewage, treated water and rivers, and his findings surprised him.

Expecting to identify a few medicinal compounds he instead found 30 of the 60 common pharmaceuticals that he surveyed. Drugs he identified included lipid-lowering drugs, antibiotics, analgesics, antiseptics, beta-blocker heart drugs, residues of drugs for controlling epilepsy as well as drugs serving as contrast agents for diagnostic X rays.

Results of recent research in North America also indicate reason for concern. At the June National Groundwater Association conference, Glen R. Boyd, a Tulane University civil engineer, reported detecting drugs in the Mississippi River, Lake Ponchetrain and in Tulane’s tap water. Boyd and his team found in tested waters low levels of clofibric acid, the pain killer naproxen and the hormone estrone. Samples of Tulane’s tap water showed estrone averaging 45 parts per trillion with a high of 80 parts per trillion.

At the recent American Chemical Society conference, Chris Metcalfe of Trent University in Ontario reported finding a vast array of drugs leaving Canadian sewage treatment plants, at times at higher levels than what is reported in Germany. Such drugs included anticancer agents, psychiatric drugs and anti-inflammatory compounds. North American treatment plants may show higher levels of pharmaceuticals because they often lack the technological sophistication of German facilities.

The U.S.G.S. is currently conducting the first nationwide assessment of “emerging contaminants” found in selected streams, including the occurrence of human and veterinary pharmaceuticals, sex and steroidal hormones and other drugs such as antidepressants and antacids. One hundred stream sites were identified, representing a wide variety of geographical and hydrogeological settings. Four of these sites are in Arizona: Santa Cruz River at Cortaro Road; Santa Cruz River near Rio Rico; Salt River below 91st Ave. sewage treatment plant; and Gila River above diversions at Gillespie Dam.

Mapping of human genome means more drugs, possibly more pollution Pharmaceuticals are greatly increasing in numbers and kinds, with greater likelihood of releases into the environment. Before the recent announcement of the almost complete categorization of the human genome, Christian G. Daughton and Thomas A. Ternes wrote in an article that appeared in Environmental Health Perspectives, “The enormous array of pharmaceuticals will continue to diversify and grow as the human genome is mapped. Today there are about 500 distinct biochemical receptors at which drugs are targeted. … The number of targets is expected to increase 20-fold (yielding 3,000 to 10,000 drug targets) in the near future.” The authors warn, “This explosion in new drugs will severely exacerbate our limited knowledge of drugs in the environment and possibly increase the exposure/effects risks to nontarget organisms.”

Stream sites were chosen that were expected to be highly susceptible to contamination by targeted compounds. Testing the sites will provide an initial indication of the potential for these compounds to enter the environment, as well provide an opportunity for developing suitable laboratory methods for measuring compounds in environmental samples at very low (sub-ppb) levels.

Detected contaminants include caffeine, which was the highest-volume pollutant, codeine, cholesterol-lowering agents, anti-depressants, and Premarin, an estrogen replacement drug taken by about 9 million women. Also chemotherapy agents were found downstream from hospitals treating cancer patients. Final results from the study are expected to be released in the fall. For additional information about the U.S.G.S. study check the website: toxics.usgs.gov/regional/emc.html

What risk does chronic exposure to trace concentrations of pharmaceuticals pose to humans or wildlife? Some scientists believe pharmaceuticals do not pose problems to humans since they occur at low concentrations in water. Other scientists say long-term and synergistic effects of pharmaceuticals and similar chemicals on humans are not known and advise caution. They are concerned that many of these drugs have the potential of interfering with hormone production. Chemicals with this effect are called endocrine disrupters and are attracting the attention of water quality experts.

To some scientists the release of antibiotics into waterways is particularly worrisome. They fear the release may result in disease-causing bacteria to become immune to treatment and that drug-resistant diseases will develop.

Scientists generally agree that aquatic life is most at risk, its life cycle, from birth to death, occurring within potentially drug-contaminated waters. For example, anti-depressants have been blamed for altering sperm levels and spawning patterns in marine life. Most studies of pharmaceutical and pharmaceutically active chemicals in water have mostly focused on aquatic animals.

For example, recent British research suggest that estrogen, the female sex hormone, is primarily responsible for deforming reproductive systems of fish, noting that blood plasma from male trout living below sewage treatment plants had the female egg protein vitellogenin. This finding would seem to be consistent with what U.S. researchers suspect has occurred downstream from treatment plants in Las Vegas and Minneapolis. Carp in these areas show the same effects as the British fish.

Some scientists believe arid regions of the West are especially vulnerable to the effects of drug-contaminated effluent. These areas are more likely to have streams that rely almost entirely on effluent for flow, especially during dry months. Further, effluent is extensively used in irrigation and even for recharging drinking water aquifers. Also, areas of the West have attracted large number of retired people who are likely to use more pharmaceuticals than other population segments; thus more pharmaceuticals in wastewater.

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Drugged Drinking Water

We should no longer think of water as a gift of nature but an industry which needs investment.
Environmental Health Perspectives Volume 108, Number 10, October 2000

Drugs and personal care products that are excreted from or washed off the body naturally end up in the sewage that flows into sewer systems and septic tanks, but where do they go from there? Scientists are beginning to monitor the extent of pharmaceutical and personal care products (PPCPs) in the aquatic environment and their consequences. What they’re finding is that, through leaching from septic tanks and escaping intact through sewage treatment processes, some of these substances are ending up back in the drinking water.

Germany has been at the forefront of PPCP monitoring. Studies conducted there during the past 10 years confirmed the presence of PPCPs in treated and untreated sewage effluent, surface water, groundwater, and drinking water. Most commonly found were anti-inflammatory and pain-killing drugs, cholesterol-lowering drugs, anticonvulsants, and sex hormones from oral contraceptives. Samples from 40 German rivers and streams turned up residues of 31 different PPCPs, according to a report presented at the March 2000 American Chemical Society meeting in San Francisco, California, by Thomas Ternes, a chemist at the Institute for Water Research and Water Technology in Wiesbaden.

Researchers worldwide have discovered more than 60 different PPCPs in water sources, according to Christian Daughton, chief of the Environmental Chemistry Branch of the U.S. Environmental Protection Agency (EPA) Environmental Sciences Division in Las Vegas, Nevada. In addition to the drugs noted above, the list includes antineoplastics, beta-blockers, bronchodilators, lipid regulators, hypnotics, antibiotics, antiseptics, X-ray contrast agents, sunscreen agents, caffeine, and fragrances such as synthetic musks. Most PPCPs are detected at concentrations ranging from parts per trillion to parts per billion, and originate in treated and untreated sewage, says Daughton, who coauthored an article on PPCPs in the December 1999 issue of EHP Supplements.

North American researchers are just beginning to look at the issue of PPCPs. Studies presented at the June 2000 Emerging Issues Conference sponsored by the National Ground Water Association, held in Minneapolis, Minnesota, indicate that the problem exists here, too. For example, environmental scientist Chris Metcalfe of Trent University in Peterborough, Ontario, detected the drugs aspirin, ibuprofen, indomethacin, bezafibrate (a cholesterol regulator), and carbamazepine (an anticonvulsant) in 10 pre- and post-treatment samples from sewage treatment plants in eastern Canada. The sewage treatment process in place removed some drugs that were easily biodegradable or more amenable to removal by activated charcoal, degradative microbes, or sand filtration, but others were resistant to degradation.

Metcalfe is just beginning to analyze the effects of cholesterol-lowering drugs, estrogens, and anticonvulsants on fish in the Great Lakes. All three drug types can potentially interfere with normal reproduction and development in fish living downstream from sewage treatment plants. His laboratory studies show that estrogen compounds at parts-per-trillion exposures feminize male fish and disrupt the development of the circulatory system, eyes, and bladder. He says it’s too soon to know whether PPCPs adversely affect wild fish populations.

In one of the first studies in the United States to report the occurrence of drugs in drinking water, environmental engineer Glen Boyd had his students at Tulane University in New Orleans, Louisiana, sample water from the Mississippi River, a local lake, and city tap water. Their preliminary experiment targeted the pain reliever naproxen, the sex hormone estrone, and clofibric acid, a major bioactive metabolite from certain anticholesterol drugs. All three were detected at varying concentrations in most of the samples. “The big unknown,” says Boyd, “[is whether PPCPs] present a health concern now or in the future.” He notes that, although the number of peer-reviewed papers on the topic is limited, government agencies concerned with water quality in the United States and professional organizations serving the water and wastewater communities are beginning to acknowledge PPCPs as an emerging environmental issue.

The long-term outcome of humans ingesting subtherapeutic doses of numerous drugs as well as any dose at all of substances not meant to be ingested remains a major unaddressed issue. “In areas of water scarcity, we’ll see more and more reuse of treated sewage to meet drinking water needs,” predicts Daughton, thereby increasing the likelihood that PPCPs will end up in drinking water. Extensive monitoring of the occurrence of PPCPs and their concentration trends over time is required to ensure safe water supplies in the future. Then toxicologists need to determine if the kinds and amounts of PPCPs that occur affect people and other living creatures. This subject will require collaboration between the Food and Drug Administration and the EPA, says Daughton, since the former usually does not address environmental concerns and the latter generally does not deal with drug issues.
-Carol Potera

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Pharmaceuticals And Endocrine Disruptors In Rivers And On Tap

Robert W. Masters
National Ground Water Association (NGWA)

Pharmaceuticals showing up in rivers downstream from sewage plants have raised concerns now that several public water systems have tested positive for drugs. Tap water in Wheeling, West Virginia, and the Ohio River tested positive for antibiotics according to USA Today November 7, 2000. A 17-year old high school student named Ashley Mulroy won the Stockholm Junior Water Prize for her project which found three common antibiotics (penicillin, tetracycline, and vancomycin) in the river and more alarming, on tap. She is not the first researcher to find drugs on tap. Thomas Heberer of the University of Berlin, Germany, presented his findings ofvarious drugs in tap water in last year’s National Ground Water Association (NGWA) international conference on emerging issues. The NGWA conference held in Minneapolis, June 7-8, 2000, was covered on Minnesota Public Radio on “Morning Edition” June 8. Keynote Speaker Janet Raloff, author of “Drugged Waters,” and Dana Kolpin of the U.S. Geological Survey were interviewed. Pharmaceuticals and endocrine disrupting chemicals in water sparked international interest as scientists from the United States (U.S.), Canada, England, and Germany attended the ground-breaking conference at the Hyatt Regency, Minneapolis. Largescale investigations are underway in over 100 of America’s rivers and streams. Current drinking water standards do not require testing for any of the over 7,000 pharmaceutical compounds being prescribed, so why bother?

DRUG RESISTANT BACTERIA
One of the dominating concerns is the creation of “Superbugs.” New strains of bacteria which are resistant to antibiotics are common near major cities and in rural areas and have been found in all 15 rivers from one study, including the Mississippi, the Ohio, and the Colorado. As bacteria is exposed to antibiotics they begin to adapt in order to survive, not unlike some of the drug resistant staph infections which have developed in hospitals. This is a concern, but like so many of today’s environmental issues, more research is needed.

HOGS DON’T DRINK COFFEE
In a society alarmed over large-scale animal feedlots termed Confined Animal Feeding Operations (CAFO), Mad Cow, and hoof-and-mouth diseases, the animal drugs have also entered the picture. Differentiating between animal and man-made contamination becomes a challenge. Human pharmaceuticals and caffeine have been used as tracers of man-made nitrate contamination (Seiler et al., 1999). If you are deciding whether a large hog lot or subdivision on septic systems caused elevated nitrate level in water wells, you might consider testing for caffeine – hogs don’t drink coffee. In Seiler’s research caffeine and prescription drugs were used as evidence that household septic tank effluent was communicating with the well.

ENDOCRINE DISRUPTING CHEMICALS (EDC) AND WILDLIFE
EDC are compounds that interfere with natural production, release, transport, metabolis m, binding, action, or elimination of hormones in the body (Ankley et al., 1998). We know that the normal functions of all organ systems are regulated by endocrine factors. Small disturbances in endocrine function, especially during certain stages of the life cycle, can lead to profound and lasting effects. There is evidence that specific populations of invertebrate, fish, avian, reptilian, and mammalian species have been, or currently are being, adversely affected by exposure to environmental contaminants that effect the endocrine systems. For example, there has been feminization of fish from waterbodies receiving discharges of municipal and some types of industrial effluents; there has been delayed or
abnormal sexual differentiation in alligators exposed to organochlorine pesticides in lakes in Central Florida; and imposex (simultaneous presence of both male and female reproductive organs) in different species of marine gastropods has been strongly correlated with exposure to tributyltin. The major groups of animals potentially at risk include fish, birds, reptiles, marine mammals, and invertebrates (Ankley et al., 1998).

MALE FISH BECAME FEMALE
As early as 1963, a scientist by the name of Yamamoto and his colleagues did numerous studies on the Japanese medaka, a freshwater fish native to southeastern Asia, in which sexual differentiation was reversed after administration of natural and synthetic hormones (Metcalfe et al., 1999b). That’s right – newborn male fish became female. While this work was done in the lab, the literature is quite clear that human sewage is altering the sex steroids in fish. Shane Snyder, a Ph.D. candidate at Michigan State, has tracked human estrogen Estradiol-17b from sewage in the Las Vegas Wash to vitellogenin induction in male fish. This protein, vitellogenin, is normally produced by reproducing females. According to Snyder, estradiol in water in the parts per trillion range can cause male fish to produce the egg making protein vitellogenin (Raloff, 1998). Vitellogenin is a recognized biomarker for exposure to estrogenic compounds. As analytical instruments become more and more precise, it is now possible to detect compounds at concentrations so minute that they were once considered insignificant. The Food and Drug Administration (FDA) requires that drug manufacturers must demonstrate that new medications have less than a part per billion concentration in the environment before they are approved or face much more stringent toxicity and risk testing (Masters, 2001).

IDENTIFYING EDC
EDC are high on the U.S. Environmental Protection Agency (EPA) radar screen. They can be natural hormones, pharmaceuticals such as birth control pills, estrogen replacement products and other steroids, and hundreds of organochlorine compounds found in pesticides and industrial chemicals like PCBs and DDT. EDC appears to be persistent in the environment and bioaccumulate, and exposures are widespread thoughout the entire globe. Examples are organochlorines, cadmium, tributyltin, alkylphenols, and estrogen. Compounds in the complex mixtures from pulp and paper mills and municipal effluents have been shown to be EDC. Actually, paper mill effluent has recently been determined to produce the male hormone Androstenedione and masculinized fish. The paper mill sludge contained the male steroid identical to the one made famous by baseball slugger Mark McGuire (Raloff, 2001). Based on recognition of the potential scope of the problem, the possibility of serious effects on the health of populations and the persistence of some EDC in the environment, research on EDC was identified as one of the six high-priority topics in the EPA Office of Research and Development Strategic Plan, U.S. EPA, 1996. U.S. EPA has developed a comprehensive plan to research endocrine disruptors (Ankley et al., 1998).

HUMAN HEALTH
The question becomes - is there a risk to human health or is there a disconnect between sound science and public perception? If you have ever heard a drug commercial on TV with a long list of side effects and “ask your doctor if it’s right for you,” it does make you wonder. Currently there are insufficient data to resolve the question of human health risk associated with pharmaceuticals in water. In general, it is thought that modest amounts of chemical exposure seldom compromise normal physiological functions. We know little about the concentrations of EDC that would induce effects in various populations. Some of the questions that must be addressed in the future are:

GROUND AND DRINKING WATERS
Is this only a surface water issue? We know from Seiler, Heberer, Ternes, and others that there is at least some data on ground water concentrations from bank infiltration at near-stream environments and septic systems. More sampling of septic tanks and wells for drugs is needed. What we do know is that drugs and EDC are in the sewage, in the rivers, and in some drinking water. Also, we want to emphasize the extremely low concentrations. We don’t find any of the 7,000 plus pharmaceutical products on the primary drinking water standards. In the United States, the number one prescribed pharmaceutical is conjugated estrogen. And at last glance estrogen, testosterone, or any other steroid hormones are also unregulated in drinking water. Early tests on treatment show promise for granular activated carbon and reverse osmosis.

NGWA CONFERENCE TO COVER PHARMACEUTICALS AND EDC
This issue of Water Resources Update is comprised of an early edition of selected manuscripts from the upcoming 2nd International Conference on Pharmaceuticals and Endocrine Disrupting Chemicals in Water, which will be held on October 9-11, 2001, in Minneapolis, Minnesota – on the Web at www.ngwa.org/-education/pharmconf.html. The conference keynote address will be given by Dr. Thomas Ternes from ESWE-Institut fur Wasserforschung and Wassertechnologie, Wiesbaden, Germany, entitled “Pharmaceuticals as New Emerging Environmental Contaminants: A Survey.”

AUTHOR
Robert “Bob” Masters is presently the Conference Coordinator at the National Ground Water Association and has produced 12 regional and international conferences on ground water. Bob is a member of the U.S. EPA National Drinking Water Advisory Council Research Working Group and the U.S. Geological Survey Advisory Committee on Water Information. He is a ground water hydrologist formerly with the U.S. Geological Survey and the former Director of the National Ground Water Information Center. He is a graduate of The Ohio State University, School of Natural Resources.

REFERENCES
- Ankley, G., E. Francis, E. Gray, R. Kavlock, S. McMaster, D. Reese, G.Sayles, A.Sergeant, & D. Vallero. (1998). Research Plan for Endocrine Disruptors. Research Triangle Park, NC, Office of Research and Development, U.S. EPA.
- Masters, Robert W. (2001). Viagra Falls: Pharmaceuticals in Rivers and Municipal Tap Water. Water Well Journal 55. no. 7: 16-18.
- Metcalfe, C.D., M. A. Gray, & Y. Kiparissis. (1999b). The Japanese Medaka (Oryzias Latipes): An In Vivo Model For Assessing The Impacts Of Aquatic Contaminants On The Reproductive Success Of Fish. In Impact Assessment of Hazardous Aquatic Contaminants Concept and Approaches. ed. S. S. Rao. 29-52. Boca Raton, FL. Lewis Publishers.
- Raloff, Janet. (1998). Drugged Waters: Does It Matter That Pharmaceuticals Are Turning Up In Water Supplies? Science News. 153. 187-189.
- Raloff, Janet. (2001). Macho Waters: Science News (Online) 169. Jan. 6, 2001.
- Seiler, R. L., S. D. Zaugg, J. M. Thomas, D. L. Howcraft. (1999). Caffeine and Pharmaceuticals as Indicators of Waste Water Contamination in Wells. Ground Water 37. no 3: 405-410.