Toby H. Galligan

Avian scavengers and the threat from veterinary pharmaceuticals

Veterinary use of the non-steroidal anti-inflammatory drug diclofenac on domesticated ungulates caused populations of resident Gyps vultures in the Indian sub-continent to collapse. The birds died when they fed on carrion from treated animals. Veterinary diclofenac was banned in 2006 and meloxicam was advocated as a ‘vulture-safe’ alternative. We examine the effectiveness of the 2006 ban, whether meloxicam has replaced diclofenac, and the impact of these changes on vultures. Drug residue data from liver samples collected from ungulate carcasses in India since 2004 demonstrate that the prevalence of diclofenac in carcasses in 2009 was half of that before the ban and meloxicam prevalence increased by 44%. The expected vulture death rate from diclofenac per meal in 2009 was one-third of that before the ban. Surveys at veterinary clinics show that diclofenac use in India began in 1994, coinciding with the onset of rapid Gyps declines ascertained from measured rates of declines. Our study shows that one pharmaceutical product has had a devastating impact on Asias vultures. Large-scale research and survey were needed to detect, diagnose and quantify the problem and measure the response to remedial actions. Given these difficulties, other effects of pharmaceuticals in the environment may remain undetected.

Diclofenac is toxic to the Steppe Eagle Aquila nipalensis: widening the diversity of raptors threatened by NSAID misuse in South Asia

Three Critically Endangered Gyps vultures endemic to South Asia continue to decline due to the use of diclofenac to treat livestock. High nephrotoxicity of diclofenac to Gyps vultures, leading to death, has been established by experiment and observation, in four out of five Gyps vulture species which occur in South Asia. Declines have also been observed in South Asia’s four other non- Gyps vulture species, but to date there has been no evidence about the importance of diclofenac as a potential cause. Neither is there any evidence on the toxicity of diclofenac to the Accipitridae other than vultures. In this study, gross and microscopic lesions and diclofenac tissue levels in Steppe Eagles Aquila nipalensis found at a cattle carcass dump in Rajasthan, India, show evidence of the toxicity of diclofenac for this species. These findings suggest the possibility that diclofenac is toxic to other accipitrid raptors and is therefore a potential threat to much wider range of scavenging species in South Asia.

Have population declines in Egyptian Vulture and Red-headed Vulture in India slowed since the 2006 ban on veterinary diclofenac?

Populations of three vulture species of the genus Gyps, the Egyptian Vulture Neophron percnopterus and Red-headed Vulture Sarcogyps calvus have declined markedly on the Indian subcontinent since the mid-1990s and all are now Critically Endangered or Endangered. Gyps vultures have been killed by the widely used non-steroidal anti-inflammatory drug diclofenac, ingested when they feed on carcasses of domesticated ungulates treated with the drug shortly before death. However, it is not known whether Egyptian Vulture and Red-headed Vulture are also sensitive to diclofenac. Veterinary use of diclofenac was banned in India in 2006. Since then, the prevalence and concentration of diclofenac in domesticated ungulates carcasses has decreased and population declines of Gyps vultures have slowed or reversed. Here, we examine counts of Egyptian and Red-headed Vultures obtained on road transects in and near protected areas between 1992 and 2011. We found indications that the declines in both species appear to have slowed and possibly increased after the ban was introduced, though the small numbers of birds counted make this conclusion less robust than that for the Gyps species. These results suggest that both species may have been adversely impacted by diclofenac and that government bans on this drug, which are beginning to take effect, may benefit a wider range of vulture species in the Indian subcontinent than was previously thought.

Metabolism of aceclofenac in cattle to vulture-killing diclofenac

The nonsteroidal anti-inflammatory drug (NSAID) diclofenac is highly toxic to Gyps vultures, and its recent widespread use in South Asia caused catastrophic declines in at least 3 scavenging raptors. The manufacture of veterinary formulations of diclofenac has since been banned across the region with mixed success. However, at least 12 other NSAIDs are available for veterinary use in South Asia. Aceclofenac is one of these compounds, and it is known to metabolize into diclofenac in some mammal species. The metabolic pathway of aceclofenac in cattle, the primary food of vultures in South Asia, is unknown. We gave 6 cattle the recommended dose of aceclofenac (2 mg/kg), collected blood thereafter at intervals for up to 12 h, and used liquid chromatography with mass spectrometry in a pharmacokinetic analysis of aceclofenac and diclofenac in the plasma. Nearly all the aceclofenac administered to the cattle was very rapidly metabolized into diclofenac. At 2 h, half the aceclofenac had been converted into diclofenac, and at 12 h four-fifths of the aceclofenac had been converted into diclofenac. Therefore, administering aceclofenac to livestock poses the same risk to vultures as administering diclofenac to livestock. This, coupled with the risk that aceclofenac may replace diclofenac in the veterinary market, points to the need for an immediate ban on all aceclofenac formulations that can be used to treat livestock. Without such a ban, the recovery of vultures across South Asia will not be successful.