ArticleToxicological sciences : an official journal of the Society of Toxicology2020
The Alginate Immobilization of Metabolic Enzymes Platform Retrofits an Estrogen Receptor Transactivation Assay With Metabolic Competence.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- Evaluations of Sex Differences in Dosimetry in Rats Following Perfluorohexanesulfonamide (PFHxSA) Oral Exposure.Toxics · 2025Article
- Assessing the impact of in vitro xenobiotic metabolism on estrogenic chemical bioactivity in high-throughput profiling assays.Toxicology · 2025Article
- Testing Strategies for Metabolite-Mediated Neurotoxicity.International journal of molecular sciences · 2025Review
- Review
- Unlocking the future of environmental safety: a framework for integrating new approach methodologies in decision-making.NAM journal · 2025Article
- Time-course characterization of whole-transcriptome dynamics of HepG2/C3A spheroids and its toxicological implications.Toxicology letters · 2024Article
- In Vitro Metabolism and p53 Activation of Genotoxic Chemicals: Abiotic CYP Enzyme vs Liver Microsomes.Chemical research in toxicology · 2024Article
- Development of a human liver microphysiological coculture system for higher throughput chemical safety assessment.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Screening for drinking water contaminants of concern using an automated exposure-focused workflow.Journal of exposure science & environmental epidemiology · 2024Article
- Increased Endocrine Activity of Xenobiotic Chemicals as Mediated by Metabolic Activation.Environmental toxicology and chemistry · 2023Article
- New Approach Methodologies for the Endocrine Activity Toolbox: Environmental Assessment for Fish and Amphibians.Environmental toxicology and chemistry · 2023Review
- Development of a bioprinter-based method for incorporating metabolic competence into high-throughputFrontiers in toxicology · 2023Article
- Article
- Mapping Mechanistic Pathways of Acute Oral Systemic Toxicity Using Chemical Structure and Bioactivity Measurements.Frontiers in toxicology · 2022Article
- High-throughput screening for identifying acetylcholinesterase inhibitors: Insights on novel inhibitors and the use of liver microsomes.SLAS discovery : advancing life sciences R & D · 2022Article
- Quantitative non-targeted analysis: Bridging the gap between contaminant discovery and risk characterization.Environment international · 2022Article
- Sourcing data on chemical properties and hazard data from the US-EPA CompTox Chemicals Dashboard: A practical guide for human risk assessment.Environment international · 2021Review
- Repeat-dose toxicity prediction with Generalized Read-Across (GenRA) using targeted transcriptomic data: A proof-of-concept case study.Computational toxicology (Amsterdam, Netherlands) · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
The U.S. EPA Endocrine Disruptor Screening Program utilizes data across the ToxCast/Tox21 high-throughput screening (HTS) programs to evaluate the biological effects of potential endocrine active substances. A potential limitation to the use of in vitro assay data in regulatory decision-making is the lack of coverage for xenobiotic metabolic processes. Both hepatic- and peripheral-tissue metabolism can yield metabolites that exhibit greater activity than the parent compound (bioactivation) or are inactive (bioinactivation) for a given biological target. Interpretation of biological effect data for both putative endocrine active substances, as well as other chemicals, screened in HTS assays may benefit from the addition of xenobiotic metabolic capabilities to decrease the uncertainty in predicting potential hazards to human health. The objective of this study was to develop an approach to retrofit existing HTS assays with hepatic metabolism. The Alginate Immobilization of Metabolic Enzymes (AIME) platform encapsulates hepatic S9 fractions in alginate microspheres attached to 96-well peg lids. Functional characterization across a panel of reference substrates for phase I cytochrome P450 enzymes revealed substrate depletion with expected metabolite accumulation. Performance of the AIME method in the VM7Luc estrogen receptor transactivation assay was evaluated across 15 reference chemicals and 48 test chemicals that yield metabolites previously identified as estrogen receptor active or inactive. The results demonstrate the utility of applying the AIME method for identification of false-positive and false-negative target assay effects, reprioritization of hazard based on metabolism-dependent bioactivity, and enhanced in vivo concordance with the rodent uterotrophic bioassay. Integration of the AIME metabolism method may prove useful for future biochemical and cell-based HTS applications.
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What OpenQuestion holds
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.