Exposure Effects of Environmentally Relevant Concentrations of the Tricyclic Antidepressant, Amitriptyline in Early Life Stage Zebrafish
dc.contributor.author | Gould, SL | |
dc.contributor.author | Winter, MJ | |
dc.contributor.author | Trznadel, M | |
dc.contributor.author | Lange, A | |
dc.contributor.author | Hamilton, CM | |
dc.contributor.author | Boreham, RJ | |
dc.contributor.author | Hetheridge, MJ | |
dc.contributor.author | Young, A | |
dc.contributor.author | Norton, WHJ | |
dc.contributor.author | Tyler, CR | |
dc.date.accessioned | 2024-07-18T16:11:59Z | |
dc.date.issued | 2024-07-11 | |
dc.date.updated | 2024-07-04T11:06:05Z | |
dc.description.abstract | Antidepressants are one of the most globally prescribed classes of pharmaceuticals, and drug target conservation across phyla means that nontarget organisms may be at risk from the effects of exposure. Here, we address the knowledge gap for the effects of chronic exposure (28 days) to the tricyclic antidepressant amitriptyline (AMI) on fish, including for concentrations with environmental relevance, using zebrafish (Danio rerio) as our experimental model. AMI was found to bioconcentrate in zebrafish, readily transformed to its major active metabolite nortriptyline, and induced a pharmacological effect (down- regulation of the gene encoding the serotonin transporter; slc6a4a) at environmentally relevant concentrations (0.03 μg/L and above). Exposures to AMI at higher concentrations accelerated the hatch rate and reduced activity levels, the latter of which was abolished after a 14 day period of depuration. The lack of any response on the features of physiology and behavior we measured at concentrations found in the environment would indicate that AMI poses a relatively low level of risk to fish populations. The pseudopersistence and likely presence of multiple drugs acting via the same mechanism of action, however, together with a global trend for increased prescription rates, mean that this risk may be underestimated using current ecotoxicological assessment paradigms. | en_GB |
dc.description.sponsorship | Innovative Medicines Initiative (IMI) Joint Undertaking | en_GB |
dc.description.sponsorship | EU’s Seventh Framework Programme | en_GB |
dc.description.sponsorship | European Federation of Pharmaceutical Industries and Associations (EFPIA) | en_GB |
dc.description.sponsorship | Merck | en_GB |
dc.description.sponsorship | University of Exeter | en_GB |
dc.identifier.citation | Awaiting citation and resolution of DOI | en_GB |
dc.identifier.doi | https://doi.org/10.1021/acs.est.3c08126 | |
dc.identifier.grantnumber | 115735 | en_GB |
dc.identifier.grantnumber | FP7/2007–2013 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/136768 | |
dc.identifier | ORCID: 0000-0002-1196-0483 | 0000-0002-3668-6564 (Winter, Matthew) | |
dc.identifier | ScopusID: 7202444342 (Winter, Matthew) | |
dc.language.iso | en | en_GB |
dc.publisher | American Chemical Society | en_GB |
dc.rights | © 2024 The Authors. Published by American Chemical Society. This publication is licensed under CC-BY 4.0. | en_GB |
dc.subject | ecotoxicology | en_GB |
dc.subject | antidepressant | en_GB |
dc.subject | pharmaceuticals | en_GB |
dc.subject | behavior | en_GB |
dc.subject | bioaccumulation | en_GB |
dc.title | Exposure Effects of Environmentally Relevant Concentrations of the Tricyclic Antidepressant, Amitriptyline in Early Life Stage Zebrafish | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2024-07-18T16:11:59Z | |
dc.identifier.issn | 0013-936X | |
dc.description | This is the final version. Available from the American Chemical Society via the DOI in this record. | en_GB |
dc.identifier.eissn | 1520-5851 | |
dc.identifier.journal | Environmental Science and Technology | en_GB |
dc.relation.ispartof | Environmental Science and Technology | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2024-06-05 | |
dcterms.dateSubmitted | 2023-11-04 | |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2024-06-05 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2024-07-04T11:06:23Z | |
refterms.versionFCD | P | |
refterms.dateFOA | 2024-07-18T16:12:09Z | |
refterms.panel | A | en_GB |
refterms.dateFirstOnline | 2024-07-11 | |
exeter.rights-retention-statement | Yes |
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