Could the environmental toxicity of diclofenac in vultures been predictable if preclinical testing methodology were applied?

Show simple item record Hassan, Ibrahim Zubairu Duncan, N.M. (Neil) Adawaren, Emmanuel Oluwasegun Naidoo, Vinny 2018-12-11T05:55:11Z 2018-12
dc.description.abstract Diclofenac, a non-steroidal anti-inflammatory pharmaceutical agent was responsible for the death of millions of Gyps vulture’s in the Indian sub-region with the safety of the other non-steroidal anti-inflammatory drugs (NSAIDs) being questionable. With preclinical safety testing not well established for avian species unlike for mammalian and environmental toxicity, we ask the question if a preclinical model could have predicted the toxic effect of the drug. For this study, we test an Organisation for Economic Co-operation and Development (OECD) guideline 223 for assessing the acute toxic potential of pesticides in birds by exposing three avian species to the drug. Exposed Japanese quails (Coturnix japonica) and Muscovy ducks (Cairina moschata) demonstrated clinical signs and pathology similar to those previously reported in vultures viz. hyperuricemia, depression, death, visceral gout and nephrosis. However, exposed domestic pigeons (Columba livia domestica) were insensitive. Following a pharmacokinetic analysis, the drug was well absorbed and distributed in the pigeons with a half-life below 6 h. A toxicokinetic evaluation in quails showed poisoning was due to metabolic constraint, with a half-life and mean residence time above 6 h and 8 h respectively resulting in death. Toxicity seen in the ducks was however not related to metabolic constraint but hyperuricemia as metabolism was rapid [half-life (1–2 h) and mean residence time (2–3 h)] irrespective of survival or death. Despite succumbing to diclofenac, the established oral median lethal dose (LD50) of 405.42 mg/kg and 189.92 mg/kg in Japanese quails and Muscovy ducks respectively from this study were substantially higher than those reported for Gyps vultures (0.098 mg/kg) which is as a result of the rapid elimination of the drug from the body in the former species. More importantly, it suggests that these species are not suitable as surrogates for non-steroidal anti-inflammatory drug toxicity testing and that the toxicity of diclofenac in vultures is idiosyncratic most likely as a result of species specific metabolism. en_ZA
dc.description.department Paraclinical Sciences en_ZA
dc.description.embargo 2019-12-01
dc.description.librarian hj2018 en_ZA
dc.description.sponsorship The University of Pretoria, South Africa en_ZA
dc.description.uri en_ZA
dc.identifier.citation Hassan, I.Z., Duncan, N., Adawaren, E.O. & Naidoo, V. 2018, 'Could the environmental toxicity of diclofenac in vultures been predictable if preclinical testing methodology were applied?', Environmental Toxicology and Pharmacology, vol. 64, pp. 181-186. en_ZA
dc.identifier.issn 1382-6689 (print)
dc.identifier.issn 1872-7077 (online)
dc.identifier.other 10.1016/j.etap.2018.10.006
dc.language.iso en en_ZA
dc.publisher Elsevier en_ZA
dc.rights © 2018 Elsevier B.V. All rights reserved. Notice : this is the author’s version of a work that was accepted for publication in Environmental Toxicology and Pharmacology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. A definitive version was subsequently published in Environmental Toxicology and Pharmacology, vol. 64, pp. 181-186, 2018. doi : 10.1016/j.etap.2018.10.006. en_ZA
dc.subject Gyps vultures en_ZA
dc.subject Diclofenac en_ZA
dc.subject Pharmacokinetics en_ZA
dc.subject Acute toxicity en_ZA
dc.subject Non-steroidal anti-inflammatory drugs (NSAIDs) en_ZA
dc.subject Lethal dose (LD50) en_ZA
dc.title Could the environmental toxicity of diclofenac in vultures been predictable if preclinical testing methodology were applied? en_ZA
dc.type Postprint Article en_ZA

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