Since the late 1990s, a steady trickle of ecological toxicity data about the fate of drugs in the environment has raised alarms among some scientists and, more recently, members of the general public. The concern is that some of the nearly 10,000 drugs currently on the market are not passive, benign travelers in the environment but instead are bioaccumulative, persistent, and toxic to wildlife—and possibly humans.
Although hormones such as synthetic estrogens and progesterones have been found to accumulate in fish at levels that disrupt reproduction, a vast majority of other drugs remain unmonitored and their long-term impacts to sensitive organisms untested (C&EN, Feb. 25, 2008, page 13).
All sorts of pharmaceuticals have been detected in the environment, from ibuprofen to Zoloft, "but we don't have a lot of information that connects their presence in the environment to effects in animals," says Duane B. Huggett, an environmental researcher at the University of North Texas. "With currently available data, the weight of evidence is that hormonally active compounds are an issue. But we need a coordinated effort to get data on a wide range of pharmaceutical classes before we know if there is a wider problem."
Drugs Of Concern:
Birth control hormones 17α-ethinylestradiol and levonorgestrel can feminize fish. Fluoxetine, or Prozac, can slow the development of fish and frogs. Carbamazepine, an anticonvulsant, affects the emergence of insects that some fish depend on for food. Diclofenac, an anti-inflammatory, has killed vultures in Pakistan
One of the easiest ways to reduce the impact of drugs in the environment would be to take a so-called benign-by-design approach, in which a drug lead's architecture would be examined for persistence, toxicity, or bioaccumulation before it went into optimization, says Klaus Kümmerer, a chemist at the University of Freiburg Medical Center, in Germany, who is developing criteria for this early consideration. "You've got to start thinking about the environment at the very beginning. It makes no sense to do the assessment after you've spent millions of dollars in development," he notes.
The question is whether medicinal chemists—who are already pruning their leads on the basis of considerations such as solubility, bioavailability, genotoxicity, pharmacokinetics, and carcinogenicity—are willing to add even more variables to their no-go list. "When I speak to our medicinal chemists about considering a benign-by-design approach, they say there's just no way they are going to further triage any leads," says a sustainability officer at a major pharmaceutical company, who requested anonymity.
David Taylor, a consultant for the pharmaceutical industry who recently retired from AstraZeneca, says that with upper management of drug companies fixated on dwindling pipelines, "there is precious little driving force" for benign-by-design drug discovery.
Getting the industry to design more environmentally friendly drugs is "going to take a combination of a carrot and regulations," adds Berkeley W. (Buzz) Cue Jr., a pharmaceutical company consultant who established Pfizer's green chemistry initiatives over a decade ago.