ArticleEnvironmental health perspectives2021
Risk Characterization and Probabilistic Concentration-Response Modeling of Complex Environmental Mixtures Using New Approach Methodologies (NAMs) Data from Organotypic
Article in Environmental health perspectives, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed.
- Probabilistic Concentration-Response Modeling and Risk Prioritization of Defined Mixtures of PFAS Using HumanEnvironmental science & technology · 2026Article
- Redefining the Health Risk of Battery Materials Through a Biologically Transformed Metal Mixture.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Challenging Additivity: Comparing Predicted and Observed AhR Activity of Polycyclic Aromatic Compound (PAC) Mixtures Containing Active and Inactive Constituents.Environmental science & technology · 2026Article
- Reducing uncertainty in dose-response assessments by incorporating Bayesian benchmark dose modeling and in vitro data on population variability.Risk analysis : an official publication of the Society for Risk Analysis · 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
- In vitro to in vivo extrapolation from 3D hiPSC-derived cardiac microtissues and physiologically based pharmacokinetic modeling to inform next-generation arrhythmia risk assessment.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Advancing Toxicity Predictions: A Review onEnvironment & health (Washington, D.C.) · 2024Review
- Combined Exposures and Mixtures Research: An Enduring NIEHS Priority.Environmental health perspectives · 2024Article
- Advancing Environmental ToxicologyEnvironment & health (Washington, D.C.) · 2024Review
- Hazard and risk characterization of 56 structurally diverse PFAS using a targeted battery of broad coverage assays using six human cell types.Toxicology · 2024Article
- Application of the Key Characteristics Framework to Identify Potential Breast Carcinogens Using Publicly AvailableEnvironmental health perspectives · 2024Article
- Wrangling Whole Mixtures Risk Assessment: Recent Advances in Determining Sufficient Similarity.Current opinion in toxicology · 2023Article
- 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
- A geospatial modeling approach to quantifying the risk of exposure to environmental chemical mixtures via a common molecular target.The Science of the total environment · 2023Article
- Beyond pharmaceuticals: Fit-for-purpose new approach methodologies for environmental cardiotoxicity testing.ALTEX · 2023Review
- Review on new approach methods to gain insight into the feto-maternal interface physiology.Frontiers in medicine · 2023Review
- Dosing Methods to Enable Cell-Based In Vitro Testing of Complex Substances: A Case Study with a PAH Mixture.Toxics · 2022Article
- Sensitive image-based chromatin binding assays using inducible ERα to rapidly characterize estrogenic chemicals and mixtures.iScience · 2022Article
- Evaluation of Metabolism of a Defined Pesticide Mixture through Multiple In Vitro Liver Models.Toxics · 2022Article
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Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
backgroundRisk assessment of chemical mixtures or complex substances remains a major methodological challenge due to lack of available hazard or exposure data. Therefore, risk assessors usually infer hazard or risk from data on the subset of constituents with available toxicity values.
objectivesWe evaluated the validity of the widely used traditional mixtures risk assessment paradigms, Independent Action (IA) and Concentration Addition (CA), with new approach methodologies (NAMs) data from human cell-based
methodsA diverse set of 42 chemicals was tested both individually and as mixtures for functional and cytotoxic effects
resultsAll mixtures showed significant bioactivity, even though some were constructed using individual chemical concentrations considered "low" or "safe." Even though CA is much more accurate as a predictor of mixture effects in comparison with IA, with CA-based POD typically within an order of magnitude of the actual mixture, in some cases, the bioactivity of the mixtures appeared to be much greater than that of their components under either additivity assumption. DISCUSSION: These results suggest that CA is a preferred first approximation for predicting mixture toxicity when data for all constituents are available. However, because the accuracy of additivity assumptions varies greatly across phenotypes, we posit that mixtures and complex substances need to be directly tested for their hazard potential. NAMs provide a practical solution that rapidly yields highly informative data for mixtures risk assessment. https://doi.org/10.1289/EHP7600.
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