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Predictive liver lipid biomarker signature of Acetyl-coenzyme A carboxylase inhibitor related developmental toxicity in non-pregnant female Han Wistar rats – Lipidomics biomarker discovery and validation by Lauraine Y. Swindale; Alexander J. Stevens; Sarah J. Whalley; Richard A. Currie; K. Michael Jessop; Florence Lai; Pei Pei Lim; Elizabeth F. McInnes; David Cowie; Aniko Kende is a Environmental Science article available to read on EtoBox.

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Introduction Acetyl-coenzyme A carboxylase (ACCase) inhibition is an attractive herbicide target. However, issues with fetal developmental toxicity identified at the late stages of the development process can halt progression of previously promising candidates. Objectives To select and verify predictive lipid biomarkers of ACCase inhibition activity in vivo using liver samples obtained from early stage 7 day repeat dose studies in non-pregnant female Han Wistar rats that could be translated to developmental toxicity endpoints discovered during late-stage studies to provide an early screening tool. Methods Liver samples from eight rat repeat dose studies, exposed to six ACCase inhibitors from three different chemistries and one alternative mode of action (MoA) that also perturbs lipid biochemistry, were analysed using liquid chromatography – high resolution accurate mass – mass spectrometry. Multivariate and univariate data analysis methods were used for biomarker discovery and validation. Results A biomarker signature consisting of sixteen lipids biomarkers were selected. Verification of the signature as indicative of ACCase inhibition was established by demonstrating consistent pe

Who reads Predictive liver lipid biomarker signature of Acetyl-coenzyme A carboxylase inhibitor related developmental toxicity in non-pregnant female Han Wistar rats – Lipidomics biomarker discovery and validation?

Author

Lauraine Y. Swindale; Alexander J. Stevens; Sarah J. Whalley; Richard A. Currie; K. Michael Jessop; Florence Lai; Pei Pei Lim; Elizabeth F. McInnes; David Cowie; Aniko Kende

Publisher

Elsevier BV

Published

2023

Language

EN

Field

Environmental Science (Physical Sciences)