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Advantages and limits of using preclinical/clinical data to predict ecotoxicological effects on wild fish : example of azole pharmaceutical compounds

Abstract : European regulation related to pharmaceuticals and pharmacovigilance require improving environmental risk assessment of these compounds. In this context, identification of biological pathways that could be disrupted in nontargeted aquatic species using qualitative preclinical/clinical data associated to toxicological data appears as a promising approach. Azole drugs is a widely used group of pharmaceutical active ingredients (APIs) characterized by a lack of data related to ecotoxicological effects. The aim of this study was to generate hypothesis about the potential ecotoxicological effects of 'azole'drugs on teleost fish. Numerous studies have reported that imidazoles and triazoles, which are used in antifungal and anti-tumoral therapies respectively, are steroidogenesis disruptors due to their adverse or therapeutic mechanism of action based on inhibition of cytochromes enzymatics complexes. However, other azole APIs such as protons pump inhibitors, carbimazole, triptans, sartans, setrons, allopurinol, aciclovir, zolpidem, theophyllin exhibit various biological activities. Pharmacodynamical data on targeted and adverse effects could allow identifying ecotoxicological effects, 'Drugs Interactions' data and 'Contraindications/Precautions for uses' data may also inform about possible mixture effects and interactions with pathological contexts. Preliminary results, qualitative pharmacological data indicate possible deleterious effects of protons pump inhibitors (benzimidazole compounds) on acid excretion and Na+ uptake in gill via interference with Na+/H+ exchanger localized in gill epithelial pavement cells, especially in hypercapnia/hypoxia contexts. These disruptions may imply deleterious consequences on vital functions as respiration, iono and osmoregulation, excretion. Results obtained for other azole drugs will be presented here and advantages and limits of this approach will be discussed.
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https://hal-ineris.archives-ouvertes.fr/ineris-00971143
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Submitted on : Wednesday, April 2, 2014 - 3:59:03 PM
Last modification on : Thursday, June 4, 2020 - 10:36:02 PM

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  • HAL Id : ineris-00971143, version 1
  • INERIS : EN-2013-116

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Olivier Cardoso, Sandrine Andres, S. Paris-Palacios, Jean-Marc Porcher, Wilfried Sanchez. Advantages and limits of using preclinical/clinical data to predict ecotoxicological effects on wild fish : example of azole pharmaceutical compounds. 23. SETAC Europe annual meeting "Building a better future : Responsible innovation and environmental protection", May 2013, Glasgow, United Kingdom. ⟨ineris-00971143⟩

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