A paper published in the scientific journal Environmental Toxicology and Pharmacology in November this year points to a new threat to vultures in Asia. Titled “Metabolism of aceclofenac to diclofenac in the domestic water buffalo Bubalus bubalis confirms it as a threat to Critically Endangered Gyps vultures in South Asia”, it presents the results of a study conducted by the Indian Veterinary Research Institute (IVRI), Bareilly, Uttar Pradesh, and collaborators.
It says that the drug aceclofenac quickly metabolises into diclofenac, the drug that was banned after it was found to be the main cause for the catastrophic decline in vulture populations across Asia, an almost 90 per cent decline in some species.
The abstract of the study says: “Vulture declines in South Asia were caused by accidental poisoning by the veterinary non-steroidal anti-inflammatory drug (NSAID) diclofenac. Although veterinary use of diclofenac has been banned, other vulture-toxic NSAIDs are legally available, including aceclofenac, which has been shown to metabolise into diclofenac in domestic cattle. We gave nine domestic water buffalo the recommended dose of aceclofenac (2 mg kg-1 body weight), collected blood at intervals up to 48 h, and carried out a pharmacokinetic analysis of aceclofenac and its metabolite diclofenac in plasma. Aceclofenac was rapidly converted to diclofenac, and was barely detectable in plasma at any sampling time. Diclofenac was present within 20 min, and peaked 4-8 h after dosing. Aceclofenac is a prodrug of diclofenac, and behaves similarly in domestic water buffalo as it did in domestic cattle, posing the same risk to vultures. We recommend an immediate ban on the veterinary use of aceclofenac across vulture-range countries.”
A dangerous drug
Diclofenac was veterinarians’ NSAID of choice to treat injured and dying cattle and domestic water buffaloes, but though the drug was effective for these animals, it had disastrous effects on vultures. As the paper says: “The catastrophic population declines of three species of Gyps vultures—white-rumped G. bengalensis, Indian G. indicus and slender-billed G. tenuirostris vultures—in South Asia from the mid-1990s onwards, was caused by accidental poisoning by the NSAID diclofenac....Ingestion of the drug by vultures when they fed on the carcasses of animals that had been treated with diclofenac prior to death resulted in kidney failure, visceral gout and death [in vultures].”
Presented with the facts, the governments of India, Pakistan, Nepal, and Bangladesh banned diclofenac. An alternative drug was at hand, and vets could easily have shifted to using meloxicam, an NSAID that is not toxic to vultures. The paper says: “Tolfenamic acid has recently been identified as another drug that is safe to vultures at doses they are likely to be exposed to in the wild. There are several other NSAIDs which are freely available and legally approved for veterinary use across vulture range states in South Asia.”
But although meloxicam and tolfenamic acid are in use, they have not completely replaced the dangerous drugs. Indeed, in some parts of India, the banned diclofenac is illegally sold as researchers from the Bombay Natural History Society (BNHS) and others proved about four years ago through an undercover operation, which Frontline had reported on. For the last four years, it has been known that aceclofenac too is lethal to vultures. This paper just proves what was already known.
And yet, the Indian government and particularly the Drugs Controller General of India (DCGI) have not acted to ban aceclofenac. The Saving Asia’s Vulture’s from Extinction (SAVE) consortium pointed out that the study’s findings were “further proof that aceclofenac, which has already been put forward over four years ago as an unnecessary threat to vultures should be totally banned, since safe alternatives (meloxicam and tolfenamic acid) are available, but despite the earlier requests to the Indian government, and an ongoing Delhi High Court case, no such action has been taken so far”. The lawyer Gaurav Kumar Bansal filed a public interest litigation petition asking the government why it had not banned the vulture-toxic drugs despite this being one of the objectives in the national Vulture Action Plan that came into being in 2006, the year that the DCGI banned diclofenac.
“Ban aceclofenac”
It is encouraging that researchers of the IVRI were the lead authors of this paper. Perhaps they should be the ones to promote the use of meloxicam and tolfenamic acid molecules as safe alternative NSAIDs. Pricing, which is normally a stumbling block, is not an issue because the cost of the safe and unsafe NSAIDs are more or less the same. Likewise, since both meloxicam and tolfenamic acid are out of patent, they can be freely manufactured. Chris Bowden, member of the Royal Society for the Protection of Birds (RSPB) and SAVE programme manager, said it was a great win-win for vultures and for pharmaceutical companies and the government and they “need to be firefighters” to save vultures. He called upon the Indian government to ban aceclofenac immediately.
A.M. Pawde, a co-author of the paper and principal scientist and incharge, IVRI, said: “This study alone gives ample evidence that aceclofenac almost immediately converts to diclofenac inside cattle and also buffalo, and is therefore a very serious threat to vultures that feed on the carcasses of any recently treated animals.”
Bivash Pandav, BHNS director, acknowledged that the Indian government demonstrated its commitment to vulture conservation when it banned veterinary diclofenac in 2006 and with its support for IVRI vulture safety testing, adding: “Such work to test the safety of these veterinary drugs for vultures is crucial, but the key step needed now is for the MoEFCC [Ministry of Environment, Forest and Climate Change] and the Drug Controller General of India to convert these findings into the necessary action—and in time to prevent their extinction, and help vultures recover from the devastating 98% declines—so they can once again play their environmental role as nature’s cleaners.”
The study’s findings were supported by others. Prof. Rhys Green of Cambridge University, UK, and SAVE chairman, added that “knowing just how lethal diclofenac is to vultures, and the devastating effect it has had, it seems like a very unfortunate loophole to allow aceclofenac to be manufactured, sold and used in veterinary use, undoing all the earlier efforts to secure India’s vultures.”
John Mallord, a senior scientist of the RSPB, said: “There really doesn’t seem any need to use veterinary aceclofenac, especially now that there are proven safe alternatives with very similar properties, like tolfenamic acid and meloxicam. We are also hopeful that paracetamol can be added to the known vulture-safe list in the near future. But some more work is needed to fully confirm this.”
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Conservationists have been urging the government not only to ban the veterinary NSAIDs that are known to be toxic to vultures but to also modify procedures whereby drugs of unknown toxicity are approved for veterinary use. Unfortunately, the Indian government has failed to respond to these urgings. The paper says that unpublished data from the BNHS shows that “sales of aceclofenac to treat injured cattle are increasing in some areas of India”. SAVE said: “This pressure has only so far been successful for one drug (apart from diclofenac) in Bangladesh, where the government recently banned veterinary use of ketoprofen.”
The paper says: “There is now sufficient evidence for governments in vulture-range states in South Asia to act, as they did for diclofenac, and immediately ban the manufacture, distribution, sale and use of bolus and injectable formulations of aceclofenac in doses suitable for large animals....Failure to act will threaten the progress that has been made supporting the partial recovery of vulture populations across South Asia.”
With scientific facts and the solution to the problem both clear, it is inexplicable why aceclofenac has still not been banned.
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