Biology subjects

Mallord, J. W.

Publications and source records attributed to Mallord, J. W..

3 recordsLinked to original sources

bioRxiv2023

Experimental safety testing confirms that the NSAID nimesulide is toxic to Gyps vultures in India

Population declines of Gyps vultures throughout South Asia were caused by unintentional poisoning by the NSAID diclofenac, which was subsequently banned. However, other vulture-toxic NSAIDs are available, including nimesulide, which, in experiments carried out in South Africa, was shown to be toxic to Gyps vultures. We report on safety-testing of nimesulide carried out on Himalayan Griffons G. himalayensis. We gave two vultures a dose of nimesulide by oral gavage at the maximum level of exposure, with two controls dosed with benzyl alcohol. In the two tested birds, plasma nimesulide concentrations peaked after six hours, while serum uric acid concentrations increased steadily up until 24 hours post-treatment, after which both birds died, displaying severe visceral gout. The control birds showed no adverse clinical or biochemical signs. We confirm that nimesulide is toxic to Gyps vultures. Veterinary use of nimesulide should be banned in all Gyps vulture range countries in the region.

pharmacology and toxicology↗

bioRxiv2021

The non-steroidal anti-inflammatory drug nimesulide kills Gyps vultures at concentrations found in the muscle of treated cattle.

Throughout South Asia, cattle are regularly treated with non-steroidal anti-inflammatory drugs (NSAIDs) and their carcasses are left for scavengers to consume. Residues of the NSAID diclofenac in cattle carcasses caused widespread mortality and catastrophic population declines in three species of Gyps vulture during the 1990s and 2000s. Diclofenac is now banned, but other NSAIDs are used in its place. Different lines of evidence, including safety testing in Gyps vultures, have shown that some of these other NSAIDs are toxic, or probably toxic, to vultures. The NSAID nimesulide is widely available and commonly used, and has been found in dead vultures with signs of renal failure (i.e. visceral gout) and without the presence of diclofenac and/or other vulture-toxic NSAIDs. Nimesulide is therefore probably toxic to vultures. Here, we report safety testing of nimesulide in Gyps vultures. In a controlled toxicity experiment, we gave two vultures the maximum likely exposure of nimesulide calculated from initial pharmacokinetic and residue experiments in cattle. Two other control birds were given an oral dose of water. Both vultures dosed with nimesulide died within 30 h, after showing outward signs of toxicity and increases in biochemical indicators of renal failure. Post-mortem examinations found extensive visceral gout in both vultures. Both control vultures survived without biochemical indicators of renal failure. With this evidence, we call for an immediate and comprehensive ban of nimesulide throughout South Asia to ensure the survival of the regions Critically Endangered vultures. More generally, testing the impacts of drugs on non-target species should be the responsibility of the pharmaceutical industry, before their veterinary use is licensed.

pharmacology and toxicology↗

bioRxiv2021

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

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 biochemical signs. Secondly, four G. himalayensis were fed tissues from water buffaloes which had been treated with double the recommended veterinary dose of tolfenamic acid prior to death and compared to two birds fed uncontaminated tissue; none suffered any clinical effects. Finally, two captive Critically Endangered vultures, one G. bengalensis and one G. Indicus, were given the MLE dose by gavage and compared to two control birds; again, none suffered any clinical effects. The death of two G. himalayensis may have been an anomaly due to i) the high dose level used and ii) the high ambient temperatures at the time of the experiment. Tolfenamic acid is likely to be safe to Gyps vultures at concentrations encountered by wild birds and could therefore be promoted as a safe alternative to toxic NSAIDs. It is manufactured in the region, and is increasingly being used to treat livestock.

pharmacology and toxicology↗