Removing the Threat of Diclofenac to Critically Endangered Asian Vultures (original) (raw)

Safety of meloxicam to critically endangered Gyps vultures and other scavenging birds in India

Animal Conservation, 2007

Widespread veterinary use of the non-steroidal anti-inflammatory drug diclofenac is responsible for the population collapse of three species of Gyps vulture in south Asia; these species are now critically endangered. Vultures die when they consume carcasses of livestock that contain lethal residues of diclofenac. National and international conservation organizations have urgently recommended that diclofenac be banned and replaced with alternative drugs that are relatively safe to Gyps vultures and other scavenging birds. We tested the safety of the NSAID meloxicam on the oriental white-backed vulture, long-billed vulture and a range of other scavenging birds in India (Egyptian vulture Neophron percnopterus, cattle egret Bubulcus ibis, house crow Corvus splendens, large-billed crow Corvus machrorhynchos and common mynah Acridotheres tristis). Meloxicam was administered by oral intubation [at 0.5 and 2.0 mg kg−1 vulture body weight (bw)], or through feeding with muscle or liver tissue (at 0.3 to 2.1 mg kg−1 vulture bw) from meloxicam-treated buffalo Bubalus bubalis. We estimate that 2.0 mg kg−1 bw is the maximum likely exposure in the wild. All 31 Gyps vultures and the 20 other scavenging birds given meloxicam survived. Feeding behaviour remained normal and there were no significant differences between the treated and control groups in body mass, or the blood haematology and biochemistry parameters monitored, including those known to be affected by diclofenac (uric acid levels and alanine transferase activity). Meloxicam is used to treat a wide range of livestock ailments and is licensed and manufactured in India. We recommend that meloxicam be introduced as rapidly as possible across the Indian sub-continent as an alternative to diclofenac.

Assessing the ongoing threat from veterinary non-steroidal anti-inflammatory drugs to Critically Endangered Gyps vultures in India

2011

Use of the veterinary drug diclofenac is responsible for bringing three species of Gyps vultures endemic to South Asia to the brink of extinction, and the Government of India banned veterinary use of the drug in May 2006. To evaluate the effectiveness of the ban we undertook surveys of. 250 veterinary and general pharmacies in 11 Indian states from November 2007 to June 2010. Twelve different classes of non-steroidal anti-inflammatory drugs (NSAIDs) were purchased from 176 pharmacies. Other than meloxicam (of negligible toxicity to vultures at likely concentrations in their food), diclofenac and ketoprofen (both toxic to vultures), little is known of the safety or toxicity of the remaining nine NSAIDs on sale. Meloxicam was the most commonly encountered drug, sold in 70% of pharmacies, but 50% of the meloxicam brands sold had paracetamol (acetaminophen) as a second ingredient. Diclofenac and ketoprofen were recorded in 36 and 29% of pharmacies, respectively, with states in western and central India having the highest prevalence of diclofenac (44-45%). Although the large number of manufacturers and availability of meloxicam is encouraging, the wide range of untested NSAIDs and continued availability of diclofenac is a major source of concern. Circumvention of the 2006 diclofenac ban is being achieved by illegally selling forms of diclofenac manufactured for human use for veterinary purposes. To provide a safer environment for vultures in South Asia we recommend reducing the size of vials of diclofenac meant for human use, to increase the costs of illegal veterinary use, and taking action against pharmaceutical manufacturers and pharmacies flouting the diclofenac ban.

Analysis of Nine NSAIDs in Ungulate Tissues Available to Critically Endangered Vultures in India

Environmental Science & Technology, 2009

In 2006, India, Pakistan, and Nepal banned the manufacture of veterinary formulations of the nonsteroidal anti-inflammatory drug (NSAID) diclofenac. This action was taken to halt the unprecedented decline of three Gyps vulture species that were being poisoned by diclofenac residues commonly present in carcasses of domestic livestock upon which they scavenged. To assess the affect of this ban and evaluate residue prevelances of other NSAIDs, we present a method to detect diclofenac and eight more NSAIDs by liquid chromatography-mass spectrometry and apply this to 1488 liver samples from carcasses of livestock taken across seven Indian states. Diclofenac was present in 11.1% of samples taken between April and December 2006, and meloxicam (4%), ibuprofen (0.6%), and ketoprofen (0.5%) were also detected. Although meloxicam is safe for a range of avian scavengers, including Gyps vultures, data regarding the safety of other NSAIDs is currently limited. If wild Gyps on the Indian subcontinent are to survive, diclofenac bans must be completely effective, and NSAIDs that replace it within the veterinary drug market must be of low toxicity toward Gyps and other scavenging birds.

The pharmacokinetics of meloxicam in vultures

Journal of Veterinary Pharmacology and Therapeutics, 2008

The pharmacokinetics of meloxicam in vultures. J. vet. Pharmacol. Therap. 31,[128][129][130][131][132][133][134] Vulture populations across the Asian subcontinent have declined dramatically in the last 15 years and are now on the verge of extinction. Although the cause of the population decline was initially unknown, the decrease has recently been conclusively linked to the use of the nonsteroidal anti-inflammatory drug diclofenac in cattle that inadvertently ended up in the vulture food chain. With the vulture numbers continuing to decline by up to 48% a year, the Indian, Nepali and Pakistan governments have recently banned the manufacture and importation of veterinary diclofenac. They have also suggested meloxicam as an alternate anti-inflammatory for use in cattle. This recommendation was based on extensive acute safety studies in the African White-backed vulture (Gyps africanus), which evaluated worst case scenarios of maximum intake based on a once in three day feeding pattern. However, the possible cumulative pharmacokinetic and pharmacodynamic effects in vultures receiving multiple daily doses of meloxicam over time were not assessed. At present very little pharmacokinetic or pharmacodynamic information is available to add further support for the safety of meloxicam in this animal species. This article discusses the oral and intramuscular pharmacokinetics of meloxicam in Cape Griffon vultures (Gyps coprotheres). Therapeutic drug monitoring was also undertaken in White-backed, Egyptian (Neophron pernopterus) and one Lappet Faced vulture (Torgos tracheliotos). In all these species, meloxicam was characterized by a short half-life of elimination. The rapid metabolism of meloxicam in combination with a short duration of effect in the studied species Gyps vultures shown in this study makes it unlikely that the drug could accumulate. This confirms the safety of repeated exposure to meloxicam in vultures of this genus.

Continuing mortality of vultures in India associated with illegal veterinary use of diclofenac and a potential threat from nimesulide

Oryx, 2015

The collapse of South Asia'sGypsvulture populations is attributable to the veterinary use of the non-steroidal anti-inflammatory drug (NSAID) diclofenac. Vultures died after feeding on carcasses of recently-medicated animals. The governments of India, Nepal and Pakistan banned the veterinary use of diclofenac in 2006. We analysed results of 62 necropsies and 48 NSAID assays of liver and/or kidney for vultures of five species found dead in India between 2000 and 2012. Visceral gout and diclofenac were detected in vultures from nine states and three species:Gyps bengalensis, Gyps indicusandGyps himalayensis. Visceral gout was found in every vulture carcass in which a measurable level of diclofenac was detected. Meloxicam, an NSAID of low toxicity to vultures, was found in two vultures and nimesulide in five vultures. Nimesulide at elevated tissue concentrations was associated with visceral gout in four of these cases, always without diclofenac, suggesting that nimesulide may have ...

Apparent Tolerance of Turkey Vultures (Cathartes Aura) to the Non-Steroidal Anti-Inflammatory Drug Diclofenac

Environmental Toxicology and Chemistry, 2008

The nonsteroidal anti-inflammatory drug diclofenac is extremely toxic to Old World Gyps vultures (median lethal dose ϳ0.1-0.2 mg/kg), evoking visceral gout, renal necrosis, and mortality within a few days of exposure. Unintentional secondary poisoning of vultures that fed upon carcasses of diclofenac-treated livestock decimated populations in the Indian subcontinent. Because of the widespread use of diclofenac and other cyclooxygenase-2 inhibiting drugs, a toxicological study was undertaken in turkey vultures (Cathartes aura) as an initial step in examining sensitivity of New World scavenging birds. Two trials were conducted entailing oral gavage of diclofenac at doses ranging from 0.08 to 25 mg/kg body weight. Birds were observed for 7 d, blood samples were collected for plasma chemistry (predose and 12, 24, and 48 h and 7 d postdose), and select individuals were necropsied. Diclofenac failed to evoke overt signs of toxicity, visceral gout, renal necrosis, or elevate plasma uric acid at concentrations greater than 100 times the estimated median lethal dose reported for Gyps vultures. For turkey vultures receiving 8 or 25 mg/kg, the plasma half-life of diclofenac was estimated to be 6 h, and it was apparently cleared after several days as no residues were detectable in liver or kidney at necropsy. Differential sensitivity among avian species is a hallmark of cyclooxygenase-2 inhibitors, and despite the tolerance of turkey vultures to diclofenac, additional studies in related scavenging species seem warranted.

Impact of Diclofenac a Non-steroidal Anti-inflammatory Veterinary Pharmaceutical Drug on Vultures

Pakistan Journal of Zoology, 2021

Roheela Yasmeen1*, Laiba Asif1 and Samia Djeffal2 1Lahore Garrison University, Lahore, Phase VI, Sector C, DHA, Lahore 2GSPA Laboratory of Research (Management of Animal Health and Productions), Institute of Veterinary Sciences,University Mentouri Brothers, Constantine 1, Constantine, Algeria Article Information Received 21 November 2019 Revised 24 May 2020 Accepted 28 July 2020 Available online 26 January 2021

Experimental safety testing shows that the NSAID tolfenamic acid is not toxic to Gyps vultures in India at concentrations likely to be encountered in cattle carcasses

2021

Population declines of Gyps vultures across the Indian subcontinent were caused by unintentional poisoning by the non-steroidal anti-inflammatory drug (NSAID) diclofenac. Subsequently, a number of other NSAIDs have been identified as toxic to vultures, while one, meloxicam, is safe at concentrations likely to be encountered by vultures in the wild. Other vulture-safe drugs need to be identified to reduce the use of those toxic to vultures. We report on safety-testing experiments on the NSAID tolfenamic acid on captive vultures of three Gyps species, all of which are susceptible to diclofenac poisoning. Firstly, we estimated the maximum level of exposure (MLE) of wild vultures and gave this dose to 38 Near Threatened G. himalayensis by oral gavage, with 15 control birds dosed with benzyl alcohol (the carrier solution for tolfenamic acid). Two birds given tolfenamic acid died with elevated uric acid levels and severe visceral gout, while the remainder showed no adverse clinical or bio...

Diclofenac poisoning is widespread in declining vulture populations across the Indian subcontinent

Proceedings of the Royal Society B: Biological Sciences, 2004

Recent declines in the populations of three species of vultures in the Indian subcontinent are among the most rapid ever recorded in any bird species. Evidence from a previous study of one of these species, Gyps bengalensis, in the Punjab province of Pakistan, strongly implicates mortality caused by ingestion of residues of the veterinary non-steroidal anti-inflammatory drug diclofenac as the major cause of the decline. We show that a high proportion of Gyps bengalensis and G. indicus found dead or dying in a much larger area of India and Nepal also have residues of diclofenac and visceral gout, a postmortem f inding that is strongly associated with diclofenac contamination in both species. Hence, veterinary use of diclofenac is likely to have been the major cause of the rapid vulture population declines across the subcontinent.