Transcriptomic pathway and benchmark dose analysis of Bisphenol A, Bisphenol S, Bisphenol F, and 3,3',5,5'-Tetrabromobisphenol A in H9 human embryonic stem cells

Peshdary, Vian; Hobbs, Cheryl A.; Maynor, Timothy; Shepard, Kim G.; Gagné, Rémi; Williams, Andrew; Kuo, Byron; Chepelev, Nikolai L.; Recio, Leslie; Yauk, Carole; Atlas, Ella

doi:10.1016/j.tiv.2021.105097

Cited by 7 publications

(2 citation statements)

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“…Comparison of the gene expression changes elicited by structurally related chemicals will substantiate the biological basis for RAX. We ( De Abrew et al, 2015 ; De Abrew et al, 2016 ; Naciff et al, 2016 ; De Abrew et al, 2019 ) and others ( Dreser et al, 2015 ; Rempel et al, 2015 ; Yeakley et al, 2017 ; Peshdary et al, 2021 ; Escher et al, 2022 ) have started trials in this direction with encouraging results. For example, we ( De Abrew et al, 2019 ) have used transcriptional profiling to identify biologically similar chemicals for m-ethyl phenol and 4-chloro-1,3-diaminobenzene, identifying m-cresol as the closest biological analogue of m-ethyl phenol; while 4-chloro-2-methylaniline hydrochloride and 2-chloro-1,4-diaminobenzene sulfate as the closest biological analogues of 4-chloro-1,3-diaminobenzene.…”

Section: Introductionmentioning

confidence: 95%

“…For example, we ( De Abrew et al, 2019 ) have used transcriptional profiling to identify biologically similar chemicals for m-ethyl phenol and 4-chloro-1,3-diaminobenzene, identifying m-cresol as the closest biological analogue of m-ethyl phenol; while 4-chloro-2-methylaniline hydrochloride and 2-chloro-1,4-diaminobenzene sulfate as the closest biological analogues of 4-chloro-1,3-diaminobenzene. Peshdary et al (2021) used transcriptional profiling to explore similarities and differences between bisphenol A (BPA) and three of its analogues, bisphenol S (BPS), bisphenol F (BPF) and 3,3′,5,5′-tetrabromobisphenol A in the human embryonic stem cell line H9 (WA09). Peshdary et al determined that BPA, BPF, and BPS have similar potencies in inducing transcriptional changes and perturb many of the same pathways, while TBBPA was the least structurally similar bisphenol of the group and had much lower potency.…”

Section: Introductionmentioning

confidence: 99%

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Article title: Transcriptional profiling efficacy to define biological activity similarity for cosmetic ingredients’ safety assessment based on next-generation read-across

et al. 2022

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The objective of this work was to use transcriptional profiling to assess the biological activity of structurally related chemicals to define their biological similarity and with that, substantiate the validity of a read-across approach usable in risk assessment. Two case studies are presented, one with 4 short alkyl chain parabens: methyl (MP), ethyl (EP), butyl (BP), and propylparaben (PP), as well as their main metabolite, p-hydroxybenzoic acid (pHBA) with the assumption that propylparaben was the target chemical; and a second one with caffeine and its main metabolites theophylline, theobromine and paraxanthine where CA was the target chemical. The comprehensive transcriptional response of MCF7, HepG2, A549 and ICell cardiomyocytes was evaluated (TempO-Seq) after exposure to vehicle-control, each paraben or pHBA, CA or its metabolites, at 3 non-cytotoxic concentrations, for 6 h. Differentially expressed genes (FDR ≥0.05, and fold change ±1.2≥) were identified for each chemical, at each concentration, and used to determine similarities. Each of the chemicals is able to elicit changes in the expression of a number of genes, as compared to controls. Importantly, the transcriptional profile elicited by each of the parabens shares a high degree of similarity across the group. The highest number of genes commonly affected was between butylparaben and PP. The transcriptional profile of the parabens is similar to the one elicited by estrogen receptor agonists, with BP being the closest structural and biological analogue for PP. In the CA case, the transcriptional profile elicited of all four methylxanthines had a high degree of similarity across the cell types, with CA and theophylline being the most active. The most robust response was obtained in the cardiomyocytes with the highest transcriptional profile similarity between CA and TP. The transcriptional profile of the methylxanthines is similar to the one elicited by inhibitors of phosphatidylinositol 3-kinase as well as other kinase inhibitors. Overall, our results support the approach of incorporating transcriptional profiling in well-designed in vitro tests as one robust stream of data to support biological similarity driven read-across procedures and strengthening the traditional structure-based approaches useful in risk assessment.

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