More drugs down the drain

Blogging on Peer-Reviewed Research
If you need the antibiotic ciprofloxacin ("cipro") (famous for its use as prophylactic agent for those potentially exposed to weaponized anthrax in 2001), I know where you can find a lot of it. In Patancheru, India, near Hyderabad, one of the world's centers for production of generic drugs. Most of the cipro made there is shipped out, but it turns out a lot of cipro stays behind, in the sewage of Patancheru. A paper by Larsson et al. (Journal of Hazardous Materials 148 (2007) 751-755; hat tip SusieF) found the highest levels in sewage effluent of pharmaceuticals of any yet reported. The champion of the many drugs-in-sewage there was cipro (up to 31,000 μg/L, higher than the maximal therapeutic level in human plasma). This is the equivalent of about 45 pounds discharged per day.

Cipro isn't the only thing found in municipal sewage. Literally tons of hormones the estrogen ethinylestradiol from oral contraceptives, ibuprofen and much else get flushed down the toilet daily after being excreted in human urine. We have no good idea what environmental effects these biologically active compounds have. The hormones are associated with feminization of fish downstream of the sewage outlets, and likely many other effects occur if we knew what to look for -- how could they not? One obvious place to look would be selection pressure on bacteria that encourages emergence of antibiotic resistance strains. We know resistant organisms can be found in these aquatic environments but we don't know if this phenomenon has public health significance (that is, affects pathogens of public health importance and then circulate in the human community).

But the Patancheru situation is likely related to the 90 or more bulk manufacturers of drugs there. In other words, the extremely high levels of active ingredients found in the effluent from a municipal sewage treatment plant serving these facilities is an industrial waste. These facilities have argued that their processes are highly controlled and designed to minimize the loss of their valuable product. This paper suggests the claims are not true.

The waste from the drug production plant doesn't get to the sewage treatment plant by pipes but is transported by trucks where it is pooled in a large cistern and held there for an average of 2 days. It undergoes various pretreaments (removal of solids, aeration) and raw domestic sewage is added to make it easier to handle. It then goes through an activated sludge process and discharged into the Isakavagu stream that feeds several larger rivers (Nakkavagu, Manjira and Godawari rivers). It was the stuff going into this stream that was sampled by the Swedish researchers.

The levels of some of the 21 pharmaceuticals were so high they were toxic to bacteria and small aquatic plants. Of course, many are antibiotics but not all organisms are sensitive and not all the drugs were antibiotics. But sewage treatment plants work by using bacteria to digest the organic matter, so one reason the levels may be so high is that the pharmaceuticals have the bacteria a fatal case of indigestion. The amount of drugs flowing into the environment is also not insignificant in terms dollar value:

The amounts of pharmaceuticals detected could be expressed in economical terms: if the equivalent amount of the 11 most abundant active substances released during 24 h were to be purchased as final products in a Swedish pharmacy, they would cost over $100,000 even if generic brands were selected. However, the production cost of the bulk drugs would apparently be much lower than the price paid by the final consumer. Since measures to minimize the release of certain drugs during production may require significant investments, a high value of the final product does not necessarily guarantee that only trace amounts would be present in the waste. (cites omitted; Larsson et al.)

In other words, if it costs more to prevent loss, it won't happen. Which is why we have environmental regulations. Without them things would be worse. You only have to travel in areas where this is little or no effective environmental regulation (like Eastern Europe or Russia) to see what it means.

Even in the US pharmaceuticals haven't yet come under regulation. We don't know if there are locations in the US comparable to Patancheru. But I wouldn't be surprised.

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Also check the sewage for bacteria that are resistant to all the latest and greatest antibiotics. And terrorists I'm sure are aware of the potential here.

Maybe I'm crazy, but this kind of stuff scares me more than Bird Flu.

Ah, but the Chinese have this figured out with regard to their own pharmaceutical firms.

They dump pharma residue into the same rivers which are already so choked with chemical toxic waste that no organism will be able to remain alive for long enough to display reactions or adaptations to the waste drugs.



Actually, in the US the EPA has started to crack down on active pharmaceuticals getting into the environment. At our hospital we are now implementing new wasting procedures for various drugs (estrogens, warfarin, and several others). While we've always had to follow high standards for getting rid of cytotoxic agents, we now have similarly stringent policies for compunds deemed to have detrimental effects on plant and animal life. Now a hospital may not have quite the potential for hazardous waste as a pharmaceutical production/storage facility, but at least it's a step.