LONDON—Pharmaceuticals in drinking water: it's a made-for-TV topic that can stir up public outcry faster than you can say "barely detectable residues."
With little data on how much excreted and dumped medicines are in the environment, and even less showing a cause-effect relationship between an active ingredient and an adverse effect, researchers, health and environmental agencies, and water-quality regulators have been playing hot potato with the question for decades. But now it's getting serious attention from the European Commission and some pharmaceutical companies. A conference convened with the University of Verona met at the Royal Society of Medicine here on Monday to discuss whether increased monitoring of medicines' effects on the environment, or "ecopharmacovigilance," warrants more intense scrutiny, and what, if anything, can be done to green an increasingly drug-dependent world.
"Pharmaceuticals are new pollutants," said Yves Levi of the University of Paris-Sud. What makes them different, he said, is that the whole point of a drug is to have a very targeted effect from the lowest dose possible. Doctors and pharmacists should keep in mind the potential for unintended exposure, said Christian Daughton of the U.S. Environmental Protection Agency, comparing drug waste in water to doctors prescribing a cocktail of unknown medications to healthy people at random.
Weighing the benefit of expensive water cleanup procedures is tough to do when you don't know much about the risk of environmental exposure. Only a few studies have shown cause-effect relationships. For instance, wide use of the animal growth promoter avoparcin, which chemically resembles vancomycin, is believed to have enabled the evolution of vancomycin-resistant enterococci, which can cause intestinal infections. And in several rivers around the world, endocrine disruptors such as ethinyl estradiol (EE2), the main component in most oral birth control pills, have been linked to the feminization of male fish. (Some research questions whether this has any effect on the fishes' ability to reproduce, however.) No studies have shown any effects on human health or on developing fetuses, potentially the biggest causes for concern.
While some governments have been concerned, E.U. leaders have not seen pharmaceutical pollution as a priority in the past. Right now, the European Commission requires an environmental risk assessment to be performed prior to drug approval. For veterinary products, approval can be denied based on environmental hazard (although this has never happened). Human medicinal product approval cannot be denied for this reason.
But Sweden, for one, is taking the issue seriously. Over the past decade, Sweden has begun monitoring the environment for approved pharmaceuticals and instituted a national classification system that ranks drugs based on their possible toxic effects and potential to build up, or bioaccumulate, in the tissues of organisms. The government disseminates this information to doctors and pharmacies (state-owned in Sweden) to encourage environmentally sound decisions. At the conference, Åke Wennmalm of the consulting agency Sustainpharma in Stockholm presented part of a new, expanded classification system that analyzes the environmental impacts of a drug—where data are available—as it travels through manufacturing, disposal, and human waste. But Sweden does not set threshold limits for any drug.
Other countries are now getting into the game. Partly in response to public demand, France recently tasked its environmental and health ministries with instituting a national action plan to reduce pharmaceuticals in the environment. The "scientific supergroup," headed by Levi, will compile a list of drugs approved in France, their toxicity, and options for risk management. The project began in May. While he welcomed government attention to environmental research, Levi said that researchers need to be careful not to overstate their concerns.
Seeing that public interest was growing, the World Health Organization (WHO) issued a report in July on pharmaceuticals in drinking water, encouraging everyone to keep a level head and encouraging more research. The report concluded that, given what is currently known, "trace quantities of pharmaceuticals in drinking water are very unlikely to pose risks to human health." It said that routine monitoring was not recommended or necessary, and, most of all, that concerns about these chemicals "should not divert the attention and valuable resources of water suppliers and regulators" from pathogenic microbes and chemicals such as lead and arsenic.
One of the conference organizers, Klaus Kuemmerer of Leuphana University in Lüneburg, Germany, said that it was a "pity" that the WHO report's headline suggests that there isn't a problem. But he emphasizes that the report calls for more research into drugs' effects on fetal development and drug interactions. All agree that upstream prevention would be best: fewer drugs should be prescribed overall, more biodegradable ones are needed, and doctors should be persuaded to favor degradable ones. Several groups, including one headed by Kuemmerer, are trying to develop more biodegradable drug products.
AstraZeneca ecotoxicologist Gisela Holm announced that the company has just begun their own ecopharmacovigilance program to monitor drugs postlaunch. This includes steps such as watching the literature, studying bioaccumulation, and being cognizant that their products may spread in environments where water standards and irrigation practices differ from those in developed countries.
If AstraZeneca's action is an indicator, regulation may be imminent. The European Commission is revising its Water Framework Directive, which is due out next year. It contains a phrase that John Fawell, an independent water-quality consultant on the WHO report, calls a catchall requirement to monitor any chemical that could be a risk. Three pharmaceuticals, the birth control chemical EE2 among them, may fall into this category.
Fawell told ScienceInsider after the meeting that he was concerned about this move to get pharmaceuticals into the updated water framework directive. "It doesn't make a lot of sense," he says. The cost of putting activated carbon filters, for instance, on effluent streams to clean them would be extraordinarily high, he says, and targeting a few drugs with these specific methods can't solve all the problems. Essentially, he says, these drugs would have to be banned. "If you take precipitous action, then you're likely to cause more problems than you're going to solve."
Frank Mastrocco, Pfizer's director of environmental toxicology, agrees. The fears about drug waste having a direct effect on the environment and suggested legislation "presupposes there is a problem," and the cost of removing substances or banning them may be "just plain impractical," he said at the meeting. For instance, if the Water Framework Directive lists EE2 as a priority hazardous substance, under its current language "emissions" of EE2—and oral birth control by proxy—would need to be phased out within 20 years. "The Vatican could get behind that, but I don't know about the rest of us," Mastrocco said. The directive's wording is "ill designed for pharmaceuticals" he says. Pharma companies would favor investigations into drugs' effects, he said, but asked that drug producers and other stakeholders be included in decision-making.
*ScienceInsider corrected this item to clarify its interpretation of a statement by Frank Mastrocco.