Non-linear transcriptional responses suggest mechanisms of tributyltin toxicity in Triops longicaudatus

Ferreira, Nuno G.C., Chessa, Adriano, Abreu, Isabel Oliveira, Cable, Joanne ORCID: https://orcid.org/0000-0002-8510-7055, Lloyd-Evans, Emyr ORCID: https://orcid.org/0000-0002-3626-1611, Carvalho, António Paulo, Guimarães, Laura and Kille, Peter ORCID: https://orcid.org/0000-0001-6023-5221 2026. Non-linear transcriptional responses suggest mechanisms of tributyltin toxicity in Triops longicaudatus. Environmental Pollution 407 , 128735. 10.1016/j.envpol.2026.128735

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Abstract

Tributyltin (TBT), a persistent biocide banned in 2008, continues to pose a significant threat to aquatic ecosystems. While its role as an endocrine disruptor is well established, its complete mechanistic cascade, particularly across environmentally relevant concentrations in non-target organisms, remains poorly characterised. Here, RNA-seq was used to characterise the transcriptional response of the non-model crustacean Triops longicaudatus following 90 min exposure to TBT at three nominal concentrations: 0.075 μg/L (96h-LC50), 0.25 μg/L (a sub-acute concentration below the US EPA acute criterion of 0.46 μg/L), and 1.54 μg/L (a high environmental concentration). Rather than following a linear concentration-response pattern, TBT showed a quantitatively validated non-linear, tri-phasic mechanistic response characterised by three distinct signatures: (1) a U-shaped immunotoxic response at sub-lethal, acute (0.075 μg/L) and high concentrations (1.54 μg/L), with the downregulation of the complement cascade; (2) a unique middle concentration (0.25 μg/L) compensatory response associated with signatures of AMPK-mediated stress mitigation, pointing to potential systemic metabolic adaptation through crustacean hyperglycemic hormone signalling and upregulation of digestive pathways; and (3) high concentration (1.54 μg/L) multi-system failure, associated with DNA repair failure, chromatin degradation and suppression of cellular quality control mechanisms including autophagy and lysosomal acidification. This collapse can be mechanistically related to endocrine dysregulation: TBT's agonism of the RXR/PPAR heterodimer simultaneously coincides with changes in ecdysone signalling whilst attenuating juvenile hormone and cholesterol biosynthesis pathways. This study presents the first comprehensive transcriptomic evidence for concentration-dependent, non-monotonic mechanistic specificity in TBT toxicity, suggesting distinct modes of cellular failure that challenge conventional toxicological paradigms and carry significant implications for environmental risk assessment and regulatory frameworks.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Biosciences
Publisher:	Elsevier
ISSN:	0269-7491
Date of First Compliant Deposit:	21 July 2026
Date of Acceptance:	7 July 2026
Last Modified:	21 Jul 2026 11:09
URI:	https://orca.cardiff.ac.uk/id/eprint/188371

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