On February 1, 2020, Watanabe, Michiko; Sasaki, Takamitsu; Takeshita, Jun-ichi; Kushida, Madoka; Shimizu, Yuki; Oki, Hitomi; Kitsunai, Yoko; Nakayama, Haruka; Saruhashi, Hitomi; Ogura, Rui; Shizu, Ryota; Hosaka, Takuomi; Yoshinari, Kouichi published an article.Quality Control of Tris(2-ethylhexyl) benzene-1,2,4-tricarboxylate The title of the article was Application of cytochrome P450 reactivity on the characterization of chemical compounds and its association with repeated-dose toxicity. And the article contained the following:
Repeated-dose toxicity (RDT) studies are one of the critical studies to assess chem. safety. There have been some studies attempting to predict RDT endpoints based on chem. substructures, but it remains very difficult to establish such a method, and a more detailed characterization of chem. compounds seems necessary. Cytochrome P450s (P450s) comprise multiple forms with different substrate specificities and play important roles in both the detoxification and metabolic activation of xenobiotics. In this study, we investigated possible use of P 450 reactivity of chem. compounds to classify the compounds A total of 148 compounds with available rat RDT test data were used as test compounds and subjected to inhibition assays against 18 human and rat P450s. Among the tested compounds, 82 compounds inhibited at least one P 450 form. Hierarchical clustering analyses using the P 450 inhibitory profiles divided the 82 compounds into nine groups, some of which showed characteristic chem. and biol. properties. Principal component analyses of the P 450 inhibition data in combination with the calculated chem. descriptors demonstrated that P 450 inhibition data were plotted differently than most chem. descriptors in the loading plots. Finally, association analyses between P 450 inhibition and RDT endpoints showed that some endpoints related to the liver, kidney and hematol. were significantly associated with the inhibition of some P450s. Our present results suggest that the P 450 reactivity profiles can be used as novel descriptors for characterizing chem. compounds for the investigation of the toxicity mechanism and/or the establishment of a toxicity prediction model. The experimental process involved the reaction of Tris(2-ethylhexyl) benzene-1,2,4-tricarboxylate(cas: 3319-31-1).Quality Control of Tris(2-ethylhexyl) benzene-1,2,4-tricarboxylate
The Article related to cytochrome chem compound repeated dose toxicity, chemical descriptors, cytochrome p450, enzyme inhibition, repeated-dose toxicity, toxicity prediction, Pharmacology: Drug Interactions and General Pharmacology and other aspects.Quality Control of Tris(2-ethylhexyl) benzene-1,2,4-tricarboxylate
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