ArticleALTEX2022
Grouping of UVCB substances with dose-response transcriptomics data from human cell-based assays.
Article in ALTEX, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 22 citations in OpenAlex.
- Carcinogens in Petroleum-derived Products: Evaluation of Benzene, Ethylbenzene, and Other Carcinogens Under High Temperatures.Safety and health at work · 2026Article
- From Reduction to Replacement: Challenges and Proposed Solutions for Animal-Free Safety Assessment of Hydrocarbon UVCB Substances.NAM journal · 2026Review
- Fetal response to maternal exposures of environmental chemicals: Utility of a four-cell human feto-maternal interface organ-on-chip.Chemico-biological interactions · 2025Article
- An approach to uncover significant direct and mediated relationships in multi-dimensional new approach methods (NAMs) data: A case study of hazard evaluation of petroleum UVCBs.The Science of the total environment · 2025Article
- Comparative Analysis of Proximal Tubule Cell Sources for In Vitro Studies of Renal Proximal Tubule Toxicity.Biomedicines · 2025Article
- Progress in toxicogenomics to protect human health.Nature reviews. Genetics · 2025Review
- Incorporating new approach methods (NAMs) data in dose-response assessments: The future is now!Journal of toxicology and environmental health. Part B, Critical reviews · 2025Review
- Comparative analysis of the physiological and transport functions of various sources of renal proximal tubule cells under static and fluidic conditions in PhysioMimix T12 platform.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Article
- Time-course characterization of whole-transcriptome dynamics of HepG2/C3A spheroids and its toxicological implications.Toxicology letters · 2024Article
- A Systematic Analysis of Read-Across Adaptations in Testing Proposal Evaluations by the European Chemicals Agency.bioRxiv : the preprint server for biology · 2024Article
- Informing Hazard Identification and Risk Characterization of Environmental Chemicals by Combining Transcriptomic and Functional Data from Human-Induced Pluripotent Stem-Cell-Derived Cardiomyocytes.Chemical research in toxicology · 2024Article
- Current frameworks for environmental and health assessment of hydrocarbon streams and products are flexible and ready for alternative non crude oil-based feeds.Toxicology research · 2024Article
- Article
- Machine Learning Methods for Endocrine Disrupting Potential Identification Based on Single-Cell Data.Chemical engineering science · 2023Article
- Application of Ion Mobility Spectrometry-Mass Spectrometry for Compositional Characterization and Fingerprinting of a Library of Diverse Crude Oil Samples.Environmental toxicology and chemistry · 2023Article
- Analysis of reproducibility and robustness of a renal proximal tubule microphysiological system OrganoPlate 3-lane 40 for in vitro studies of drug transport and toxicity.Toxicological sciences : an official journal of the Society of Toxicology · 2023Article
- Article
- A tiered testing strategy based on in vitro phenotypic and transcriptomic data for selecting representative petroleum UVCBs for toxicity evaluation in vivo.Toxicological sciences : an official journal of the Society of Toxicology · 2023Article
- Analytical chemistry solutions to hazard evaluation of petroleum refining products.Regulatory toxicology and pharmacology : RTP · 2023Review
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
The application of in vitro biological assays as new approach methodologies (NAMs) to support grouping of UVCB (unknown or variable composition, complex reaction products, and biological materials) substances has recently been demonstrated. In addition to cell-based phenotyping as NAMs, in vitro transcriptomic profiling is used to gain deeper mechanistic understanding of biological responses to chemicals and to support grouping and read-across. However, the value of gene expression profiling for characterizing complex substances like UVCBs has not been explored. Using 141 petroleum substance extracts, we performed dose-response transcriptomic profiling in human induced pluripotent stem cell (iPSC)-derived hepatocytes, cardiomyocytes, neurons, and endothelial cells, as well as cell lines MCF7 and A375. The goal was to determine whether transcriptomic data can be used to group these UVCBs and to further characterize the molecular basis for in vitro biological responses. We found distinct transcriptional responses for petroleum substances by manufacturing class. Pathway enrichment informed interpretation of effects of substances and UVCB petroleum-class. Transcriptional activity was strongly correlated with concentration of polycyclic aromatic compounds (PAC), especially in iPSC-derived hepatocytes. Supervised analysis using transcriptomics, alone or in combination with bioactivity data collected on these same substances/cells, suggest that transcriptomics data provide useful mechanistic information, but only modest additional value for grouping. Overall, these results further demonstrate the value of NAMs for grouping of UVCBs, identify informative cell lines, and provide data that could be used for justifying selection of substances for further testing that may be required for registration.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.