science/technology Daughton organized the session with Thomas A. Ternes, a research chemist with the Institute for Water Research & Water Technology, which is part of the water company in Wiesbaden, Germany. Their goal, Daughton said, was to "catalyze and promote further discussion" of the issue. Of the 17 presentations made, 11 were from researchers based in Europe, "where research has progressed further and faster," Daughton said. The symposium's emphasis was on the consequences of the use and disposPamela S. Zurer potential effects on aquatic organisms al of drugs and personal care products by individuals, not on the actions of and other wildlife are virtually unknown. C&EN Washington "Pharmaceuticals and personal care manufacturers, whose waste streams products as pollutants is not something are better defined and controlled, From the ACS meeting people think about, but anything we use Daughton noted. In the U.S., the topic ost people don't think twice ends up in the environment," said Chris- falls in between the regulatory responsiabout tossing their old medica- tian G. Daughton, chief of the Environ- bilities of EPA and the Food & Drug tions and perfumes into the mental Protection Agency's environ- Administration. trash or down the toilet. They don't wor- mental chemistry branch of the Envi"The purpose of the symposium is to ry about where their aftershave ends up ronmental Sciences Division in Las get a scientific dialogue going," Daughafter they shower or what happens to Vegas. ton said. 'We need to rule in or rule out their sunscreen as they swim. And they "Anything you put on your skin, any- if this is an environmental problem or certainly don't dwell on the ultimate fate thing you ingest, is eventually excreted not." of the prescription and over-the-counter and ends up in the sewage," Daughton Pharmaceuticals enter the environdrugs they take. added. "Little is known about the ef- ment mostly through sewage, whether Yet according to scientists who fects. There are many unanswered raw or treated. Portions of most drugs spoke at a Division of Environmental questions because the focus of environ- ingested—whether prescription, overChemistry symposium at last month's mental chemists has been on persistent the-counter, or illegal—are excreted in American Chemical Society national chemical pollutants" such as dioxins or the urine or feces. The portion that is metabolized sometimes yields metabomeeting in San Francisco, such chemi- polychlorinated biphenyls (PCBs). lites that are still bioactive cals are contaminating ——-—— or conjugates that can be the environment. At a — — — converted back to the origdaylong session titled Variety of pharmaceuticals, fragrances have inal active compound. In "Pharmaceuticals and been identified in the environment addition, people flush their Personal Care Products unused or expired medicain the Environment: An tions down the toilet or Emerging Concern," Euadd them to the trash, ropean researchers prewhere they can leach out sented data confirming of landfills. that a wide variety of Clofibric acid Carbamazepine drugs and their metaboVeterinary drugs and Metabolite of lipid regulators Antiepileptic lites are showing up in low food additives also are concentrations in the washowing up in the enviterways of Germany, Switronment. Those comzerland, Croatia, and pounds end up in animal H Greece. The situation may urine and manure, where be the same in the U.S., they can be washed into but that can only be sursurface waters. Sulfamethoxazole Diclofenac sodium mised because of a lack of Human and veterinary antibiotic Nonsteroidal anti-inflammatory In preparing a recent monitoring data—despite review, Daughton and the compounds' designed Ternes found that some 50 biological activity. individual pharmaceuticals and ingredients from perThe chemicals in quessonal care products or their tion are already being metabolites from 10 broad used by humans at much classes have been identihigher concentrations, so fied in environmental samany risk to human health Galaxolide lopromide ples [Environ. Health Perfrom environmental expoSynthetic musk X-ray contrast media spect. SuppL, 107, 907 sure is minimal. But the
DRUGS DOWN THE DRAIN
Surprisingly little research exists on the potential environmental effects of pharmaceuticals and personal care products
M
oJOQC
jy
APRIL 10,2000 C&EN
51
seience If Your Work Involves Basic Research on Drug Development, Drug Discovery, or the Synthesis of New Organic Molecules . . . Register Today for This ACS Short Course:
State-of-the-Art
Antibiotics and Antibacterial Agents June 27-29, 2000 - Philadelphia, PA %
Obtain Up-to-the-Minute Aid Your Research
Information to
Understand how bacteria are infected by antibiotics and how drugs select for drug resistance Learn how and why various antibacterial targets are chosen for drug development Find out how new technologies are advancing the drug discovery process Learn how changes to the structures of small natural products can be done by genetic rather than chemical means Understand the exciting biochemistry involved in the mechanism of action of quinolones AND MUCH MORE! Course Director: Daniel T. Chu, Director, Antibacterial Research and Medicinal Chemistry, Chiron Corporation. Register Today! Call the ACS Short Courses Office at (800) 227-5558, ext 4508, or at (202) 872-4508, or visit our website at
www.acs.org/shortcourses For more information, fax or mail the coupon below YES! Please send me a brochure describing the Antibiotics and YES! Antibacterial Agents short course to be offered June 27-29, 2000 in Philadelphia, PA. NAME. TITLE _ ORGANIZATION _ ADDRESS CITY, STATE, ZIP_ PHONE FAX E-MAIL .
Mail to: American Chemical Society, Dept. of Continuing Education, 1155 Sixteenth Street NW, Washington, DC 20036. E-mail to:
[email protected]. Fax to: (202)872-6336.
52
APRIL 10,2000 C&EN
Ternes: drugs, metabolites are In effluent
(1999)]. But "the literature is silent on many other widely used classes of drugs," Daughton said, either because no one has looked for them or because researchers haven't reported that they looked for a particular compound and didn'tfindit. In Germany, Ternes' laboratory has developed analytical methods that can quantify more than 80 different analytes, including drugs, hormones, and metabolites. The researchers found 36 of 55 pharmaceuticals and five of nine metabolites in at least one German sewage treatment plant's effluent. The highest concentrations of drugs Ternes and coworkers identified were for the antiepileptic carbamazepine, with a maximum of about 6 ug per L. They quantified even higher amounts (11 \xg per L) of iodinated compounds like Iopromide, which are used in hospitals as X-ray contrast media. The concentrations of such compounds are significantly lower in German rivers, Ternes reported—generally in nanograms per liter. But small streams tend to be much more highly contaminated than big rivers, he said, because the lower volume of flow in small streams is not able to dilute sewage treatment plant effluent as much. Human consumption isn't the only source of drugs found in the environment. A Swiss study found high levels of veterinary antibiotics in two lakes in the region of Switzerland with the highest density of animals, Norriel S. Napales told the symposium. Napales is a postdoctoral researcher in the laboratory of chemistry professor Walter Giger at the
Daughton: rule In or rule out a problem
Swiss Federal Institute for Environmental Science & Technology, Diibendorf. The large amounts of sulfonamides— antibiotics used in animal feed—suggested to the researchers that it might be coming from runoff of land adjacent to the lakes. In Germany, Ternes generally did not find drugs or metabolites in drinking water in his studies. But that's not the case in Berlin, according to Thomas Heberer of the Institute of Food Chemistry at the Technical University of Berlin. Heberer showed a chromatogram of a sample of his own tap water. It contained nanogram-per-liter concentrations of clofibric acid, a metabolite of several prescription lipid regulators, and diclofenac, a nonsteroidal antiinflammatory agent. "As a friend of mine said," Heberer told the symposium, "even if there's no toxicological problem, it makes you a little uncomfortable to know you are drinking something that's been through someone else's kidneys." Berlin is a worst-case situation, Heberer emphasized. The highly populated urban region contains only small rivers with relatively low flow. In the dry summer, treated sewage discharge becomes a large fraction of the river flow not far from intake sources for drinking water. Heberer also described studies on synthetic musks—compounds used in perfumes and as fragrances in, for example, laundry detergent. In the Tetlow Canal that runs through Berlin, Heberer and his coworkers found much higher concentrations of polycyclic musks
than they had of pharmaceuticals. The fat-soluble musks are more difficult to degrade than most drugs and could accumulate in the food chain. Indeed, data from more than 2,000 fish taken from rivers, lakes, and canals in Berlin indicate significant accumulation, Heberer reported. For example, an average of 1.48 mg per kg of the synthetic musk Galaxolide was found in eels. Although most other drugs and personal care products degrade much more rapidly than do the musks, they can act as long-lived pollutants because they are continually being replenished, Daughton pointed out. Yet almost nothing is known about how continuous exposure might affect wildlife, especially aquatic organisms that are literally bathing in the trace contaminants. Pharmaceuticals and personal care products could have effects even at very low concentrations, suggested David Epel, professor of marine sciences at Stanford University's Hopkins Marine Station in Pacific Grove, Calif. The compounds could overwhelm organisms' "efflux" transporters, their first line of defense against toxins, he pointed out. These adenosine triphosphate-dependent transporters actively remove compounds from cells. 'They are working all the time to keep natural toxins out of cells," he said. "But if you have a lot of chemicals in the environment, they can compete and compromise that first line of defense. That's potential bad news." Certain drugs, such as P-channel blockers and immunosuppressants, are already known to inhibit the transporters. 'There's an urgent need for research to determine whether measurable levels [of pharmaceuticals and personal care products] could affect transporters and compromise the health of organisms," Epel said. 'The effect may be very subtle." Daughton said he hoped increased attention to the issue would lead to a better understanding of the complex interconnectedness between humans and the environment. "We're connected to the environment very closely in everything we do," he said. "Pharmaceuticals and personal care products are used throughout the world by a huge number of people. All these small point discharges are adding up. Each individual can have an effect on the environment."^
One of these molecules is not like the others.
mm
Did you find it? Subtle, isn't it? At Shearwater Polymers we've made dramatic improvements in drug efficacy and dosing through molecular camouflage. With 14 clinical trials in progress for nine polymer-modified products and three Phase III trials complete, Shearwater Polymers provides clinically proven technology for enhanced drug efficacy, solubility and stability. Shearwater's Drug Delivery Division, in conjunction with the Operations Division, offers the world's only "one-stop-shop" for the attachment of polyethylene glycol) to pharmaceuticals, medical devices and in vivo diagnostics. Fundamental Research through to cGMP manufacturing.
We Can Do It. enhancing medicine's future
SHEARWATER /SH POLYMERS9 1112 Church Street Huntsville, Alabama 35801 800 457-1806 256 533-4805/ax
[email protected] e-mail swpolymers.com CIRCLE 30 ON READER SERVICE CARD
APRIL 10, 2000 C&EN
53
