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Indian drug manufacturers must clean up their act

By Kirsty Barnes , 28-Aug-2007

New research has branded pharmaceutical manufacturers in India as being responsible for the release of substantial and worrying amounts of active pharmaceutical ingredients (APIs) into the environment.

The results have prompted Swedish researchers to call for "extended investigations on the effluent quality, including the release of APIs, from production facilities in different regions of the world", fearing the problem detected in India could be the tip of the iceberg.

 

 

 

"The study demonstrates that there are production facilities that release substantial amounts of drugs to the aquatic environment…at present it is not possible to say how widespread the problem is".

 

 

The team of scientists from Goteborg University tested the levels of APIs contained in effluent from a wastewater treatment plant serving about 90 bulk drug manufacturers in Patancheru, near Hyderabad - a major production site of generic drugs for the world market.

 

 

 

They hypothesised that treated waste from such sites, which eventually ends up in local waterways, could be underrated as a "substantial environmental concern."

 

 

 

Prior to the study, it was generally accepted that the main route for such drugs to enter the aquatic environment was via sewage treatment plants receiving wastewater from households and hospitals. The levels detected in such effluents have only been from below 1ng/L up to a few µg/L.

 

 

 

However, in the Swedish study, the water samples from India were screened by a Swedish contract laboratory for the presence of 59 pharmaceuticals, the results indicating that 21 of these were present at concentrations above 1µg/L.

 

 

 

In addition, the lab quantified the levels of the nine most abundant drugs in addition to two additional fluoroquinolones, and also conducted standard toxicity tests, which showed these 11 drugs were present in levels above 100µg/L - in some cases, well above.

 

 

 

The antibiotic ciprofloxacin (a fluoroquinolone) showed levels of 28,000-31,000µg/L; iosartan, an angiotensin II receptor antagonist was measured at 2,400-2,500µg/L; the H1-receptor antagonist cetirizine was 1,300-1,400µg/L; metoprolol, a ß1-adrenoreceptor antagonist came in at 800-950 µg/L; the antibiotic enrofloxacin (a fluoroquinolone) showed levels of 780-900µg/L; citalopram, a serotonin reuptake inhibitor was 770-840µg/L; and the two antibiotics norfloxacin and llmefloxacin (both fluoroquinolones) were recorded at levels of 390-420µg/L and 50-300µg/L respectively.

 

 

 

"To the best of our knowledge, the concentrations of these 11 drugs were all above the previously highest values reported in any sewage effluent," wrote the researchers, who added that they were unaware of such information having been previously reported in any peer-reviewed literature.

 

 

 

"We would like to highlight the exceptional concentrations of fluoroquinolones found here, particularly ciprofloxacin - an antibiotic produced by several companies in the area".

 

 

Normally, all of these drugs, including ciprofloxacin, are found in sewage effluents at concentrations around or below 1µg/L and occasionally at somewhat higher levels in discharges from hospitals, they explained.

 

 

 

"The concentrations of ciprofloxacin were higher than the maximal therapeutic human plasma levels," wrote the researchers in their report, titled: "Effluent from drug manufactures contains extremely high levels of pharmaceuticals" and published in the Journal of Hazardous Materials on 6 July.

 

 

 

Providing a further analogy, they said that "the discharge load of ciprofloxacin corresponds to approximately 45 kg of API per day, which is equivalent to the total amount consumed in Sweden (population nine million) over an average 5-day period".

 

 

The scientists said that the high levels of several broad-spectrum antibiotics detected in the effluent raise concerns about the development of resistance to such drugs in the local environment. In addition, the diverse list of other drugs detected in high concentrations is also alarming:

 

 

 

"For most of these there is yet insufficient chronic effects data on organisms likely to have highly conserved target molecules with humans (i.e. fish) to make adequate risk assessments".

 

 

"For example, citalopram is known to affect the behaviour of fish but the dose-response relationship remains to be established", they said.

 

 

 

Meanwhile, the treated effluent studied "does not constitute the only, or even worst, contribution to environmental pollution by local industries in Patancheru. Dumping of untreated industrial waste is a recognised problem", the researchers added.

 

 

 

Indeed, in this area of India for example, drug manufacturers are only allowed to dispose of only a certain amount of waste per day, and if its chemical concentration is too high, the company is fined. However, these fines are reportedly so small that they are virtually ineffective as a deterrent.

 

 

 

It has also been reported that some companies with excessive amounts of waste to dispose of do so illegally by dumping it in secluded areas of countryside or waterways.

 

 

 

India is the largest offshore ingredients supplier to pharmaceutical manufacturers in the West. In the hope that industry bigwigs and governments will take note, the scientists stressed that "the environmental impact of the [drug] production is not only a matter of local concern".

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