ArticleToxicological sciences : an official journal of the Society of Toxicology2023
Per- and polyfluoroalkyl substances (PFAS) in mixtures show additive effects on transcriptomic points of departure in human liver spheroids.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 44 citations in OpenAlex.
- Liver organoids for chemical risk assessment: biological fidelity, standardization, and context-of-use frameworks.Archives of pharmacal research · 2026Review
- Probabilistic Concentration-Response Modeling and Risk Prioritization of Defined Mixtures of PFAS Using HumanEnvironmental science & technology · 2026Article
- PFAS Mixture Composition and Internal Exposure Profiles Shape Biological Responses under Field-Realistic Exposure.Environmental science & technology · 2026Article
- Identification of functional genetic components modulating toxicity response to PFOS using genome-wide CRISPR screens in HepG2/C3A cells.Archives of toxicology · 2026Article
- Mechanism-based new approach methodologies for in vitro detection of chemical-induced liver steatosis.Archives of toxicology · 2026Review
- The Placenta as a Target Organ for Poly- and Perfluoroalkyl Substances (PFASs): Molecular Mechanisms of Toxicity.International journal of molecular sciences · 2026Review
- Challenging Additivity: Comparing Predicted and Observed AhR Activity of Polycyclic Aromatic Compound (PAC) Mixtures Containing Active and Inactive Constituents.Environmental science & technology · 2026Article
- Embryotoxicity and mixture effects of legacy PFAS in a human iPSC-based 3D model.Cell biology and toxicology · 2026Article
- Advancing chemical mixture toxicity assessment using advanced in vitro NAMs: current status and future perspectives.Frontiers in toxicology · 2026Review
- Perfluorooctane sulfonate (PFOS) in follicular fluid and human granulosa cell dysfunction: a physiologically based toxicokinetic model translation of long-term low-levelHuman reproduction open · 2026Article
- Rapid behavioral screening in the planarianFrontiers in toxicology · 2026Article
- Identification of Functional Genetic Components Modulating Toxicity Response to PFOS using Genome-wide CRISPR Screens in HepG2/C3A cells.bioRxiv : the preprint server for biology · 2025Article
- Comparative transcriptomic analysis of perfluoroalkyl substances-induced responses of exponential and stationary phase Escherichia coli.BMC genomics · 2025Article
- High-throughput transcriptomics analysis of equipotent and human relevant mixtures of BPA alternatives reveal additive effects in vitro.Archives of toxicology · 2025Article
- Identification of four mechanisms of toxicity for per- and polyfluoroalkyl substances through transcriptomic profiling in human liver spheroids exposed to 24 PFAS.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Exposure to per- and poly-fluoroalkyl substances in association to later occurrence of type 2 diabetes and metabolic pathway dysregulation in a multiethnic US population.EBioMedicine · 2025Article
- Extracellular Vesicle (EV) Mechanisms of Toxicity for Per and Polyfluoroalkyl Substances: Comparing Transcriptomic Points of Departure Across Global Versus EV Regulatory Gene Sets.Environmental and molecular mutagenesis · 2025Article
- Enhanced spatial analysis assessing the association between PFAS-contaminated water and cancer incidence: rationale, study design, and methods.BMC cancer · 2025Article
- 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
- Advancing human health risk assessment: the role of new approach methodologies.Frontiers in toxicology · 2025Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Per- and polyfluoroalkyl substances (PFAS) are a wide range of chemicals that are used in a variety of consumer and industrial products leading to direct human exposure. Many PFAS are chemically nonreactive and persistent in the environment, resulting in additional exposure from water, soil, and dietary intake. While some PFAS have documented negative health effects, data on simultaneous exposures to multiple PFAS (PFAS mixtures) are inadequate for making informed decisions for risk assessment. The current study leverages data from previous work in our group using Templated Oligo-Sequencing (TempO-Seq) for high-throughput transcriptomic analysis of PFAS-exposed primary human liver cell spheroids; herein, we determine the transcriptomic potency of PFAS in mixtures. Gene expression data from single PFAS and mixture exposures of liver cell spheroids were subject to benchmark concentration (BMC) analysis. We used the 25th lowest gene BMC as the point of departure to compare the potencies of single PFAS to PFAS mixtures of varying complexity and composition. Specifically, the empirical potency of 8 PFAS mixtures were compared to predicted mixture potencies calculated using the principal of concentration addition (ie, dose addition) in which mixture component potencies are summed by proportion to predict mixture potency. In this study, for most mixtures, empirical mixture potencies were comparable to potencies calculated through concentration addition. This work supports that the effects of PFAS mixtures on gene expression largely follow the concentration addition predicted response and suggests that effects of these individual PFAS in mixtures are not strongly synergistic or antagonistic.
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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.