A clinical chemical atlas of xenobiotic toxicity for the Sprague–Dawley rat
File(s)
Author(s)
Type
Journal Article
Abstract
The Consortium for Metabonomic Toxicology (COMET) studies was designed to model metabolic responses to organ- and mechanism-specific toxins to predict acute drug toxicity in rats. A range of clinical chemical parameters were measured in 7-day toxicology studies for 86 toxins eliciting a range of organ- and mechanism-specific effects. Additionally, 21 surgical or physiological stressors were evaluated to identify physiological or metabolic responses that might confound the interpretation of observed toxicity profiles. From these studies on a total of 3473 rats measured at six pharmaceutical companies, we provide a set of 12 serum and 5 urine physical and clinical chemistry parameters. Samples were collected at 24 h, 48 h and 168 h post-dose for each animal and are presented as a downloadable database file. We also summarise the main observations based on the group response at the level of the individual toxin. We demonstrate that correlations between parameters, such as serum bilirubin and aspartate aminotransferase (AST), provide a more nuanced profile of organ-specific toxicity than consideration of individual parameters alone. In addition, we highlight the variability in the measured parameters across the dataset attributable to inter-laboratory differences, and the heterogeneity of metabolic responses to particular compounds or differences in temporal patterns of response. This clinical chemistry atlas of toxicity serves as a valuable reference tool for evaluating the potential toxicity of novel drug candidates.
Date Issued
2025-06-01
Date Acceptance
2025-02-24
Citation
Archives of Toxicology, 2025, 99 (6), pp.2669-2681
ISSN
0340-5761
Publisher
Springer Science and Business Media LLC
Start Page
2669
End Page
2681
Journal / Book Title
Archives of Toxicology
Volume
99
Issue
6
Copyright Statement
© The Author(s) 2025 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
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Subjects
Animals
Rats
Rats, Sprague-Dawley
Bilirubin
Aspartate Aminotransferases
Xenobiotics
Female
Male
Metabolomics
Toxicity Tests, Acute
Publication Status
Published
Date Publish Online
2025-05-06