Mapping Mechanistic Pathways of Acute Oral Systemic Toxicity Using Chemical Structure and Bioactivity Measurements.
acute oral systemic toxicity
adverse outcome pathway
chemical structure-based clustering
in vitro bioactivity assays
new alternative methods
tiered testing
tiered testing strategy
Journal
Frontiers in toxicology
ISSN: 2673-3080
Titre abrégé: Front Toxicol
Pays: Switzerland
ID NLM: 101777990
Informations de publication
Date de publication:
2022
2022
Historique:
received:
28
11
2021
accepted:
31
01
2022
entrez:
17
3
2022
pubmed:
18
3
2022
medline:
18
3
2022
Statut:
epublish
Résumé
Regulatory agencies around the world have committed to reducing or eliminating animal testing for establishing chemical safety. Adverse outcome pathways can facilitate replacement by providing a mechanistic framework for identifying the appropriate non-animal methods and connecting them to apical adverse outcomes. This study separated 11,992 chemicals with curated rat oral acute toxicity information into clusters of structurally similar compounds. Each cluster was then assigned one or more ToxCast/Tox21 assays by looking for the minimum number of assays required to record at least one positive hit call below cytotoxicity for all acutely toxic chemicals in the cluster. When structural information is used to select assays for testing, none of the chemicals required more than four assays and 98% required two assays or less. Both the structure-based clusters and activity from the associated assays were significantly associated with the GHS toxicity classification of the chemicals, which suggests that a combination of bioactivity and structural information could be as reproducible as traditional
Identifiants
pubmed: 35295211
doi: 10.3389/ftox.2022.824094
pii: 824094
pmc: PMC8915918
doi:
Types de publication
Journal Article
Langues
eng
Pagination
824094Informations de copyright
Copyright © 2022 Edwards, Nelms, Hench, Ponder and Sullivan.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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