Derivation of metabolic point of departure using high-throughput in vitro metabolomics: investigating the importance of sampling time points on benchmark concentration values in the HepaRG cell line.

ABSTRACT: Amongst omics technologies, metabolomics should have particular value in regulatory toxicology as the measurement of the molecular phenotype is the closest to traditional apical endpoints, whilst offering mechanistic insights into the biological perturbations. Despite this, the application of untargeted metabolomics for point-of-departure (POD) derivation via benchmark concentration (BMC) modelling is still a relatively unexplored area. In this study, a high-throughput workflow was applied to derive PODs associated with a chemical exposure by measuring the intracellular metabolome of the HepaRG cell line following treatment with one of four chemicals (aflatoxin B₁, benzo[a]pyrene, cyclosporin A, or rotenone), each at seven concentrations (aflatoxin B₁, benzo[a]pyrene,

SUBMITTER: Malinowska JM 

PROVIDER: S-EPMC9968698 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature