ArticleToxicological sciences : an official journal of the Society of Toxicology2022
Are Non-animal Systemic Safety Assessments Protective? A Toolbox and Workflow.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
26 citing papers in PubMed, 60 citations in OpenAlex.
- NGRA in Cosmetic Safety: Moving From the Frameworks and Case Studies to Wide Adoption.Current opinion in toxicology · 2026Article
- PBK modelling of phthalates and their metabolites and the application in next generation risk assessment.Archives of toxicology · 2026Article
- Integration of in vitro and in silico approaches enables prediction of drug-induced liver injury.Archives of toxicology · 2026Article
- Quantitative estimates of inter-individual variability for new approach methodologies-based systemic safety toolbox using a population-based human in vitro model.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- The way forward for assessing the human health safety of cosmetics in the EU: Proceedings of Workshop 2.Archives of toxicology · 2026Article
- A Novel Workflow for Non-Animal PBK Modelling of UV Filters: Oxybenzone as a Case Study.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Establishing scientific confidence in a two-chamber co-culture system to evaluate androgenic response in the presence of hepatic metabolism.Toxicology letters · 2025Article
- Optimizing the implementation of safe and sustainable by design to better enable sustainable innovation.iScience · 2025Review
- 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
- Integrating Transcriptomic and Targeted New Approach Methodologies into a Tiered Framework for Chemical Bioactivity Screening.Environmental health perspectives · 2025Article
- Deciphering per- and polyfluoroalkyl substances mode of action: comparative gene expression analysis in human liver spheroids.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Advancing systemic toxicity risk assessment: Evaluation of a NAM-based toolbox approach.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Sensitivity Analysis of the Inputs for Bioactivity-Exposure Ratio Calculations in a NAM-Based Systemic Safety Toolbox.NAM journal · 2025Article
- Evaluation of a non-animal toolbox informed by adverse outcome pathways for human inhalation safety.Frontiers in toxicology · 2025Article
- Highlighting best practices to advance next-generation risk assessment of cosmetic ingredients.NAM journal · 2025Article
- An advancement in developmental and reproductive toxicity (DART) risk assessment: evaluation of a bioactivity and exposure-based NAM toolbox.Frontiers in toxicology · 2025Article
- New approach methodologies (NAMs): identifying and overcoming hurdles to accelerated adoption.Toxicology research · 2024Review
- Enabling novel paradigms: a biological questions-based approach to human chemical hazard and drug safety assessment.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Combination of computational new approach methodologies for enhancing evidence of biological pathway conservation across species.The Science of the total environment · 2024Article
- Protecting Human and Animal Health: The Road from Animal Models to New Approach Methods.Pharmacological reviews · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
An important question in toxicological risk assessment is whether non-animal new approach methodologies (NAMs) can be used to make safety decisions that are protective of human health, without being overly conservative. In this work, we propose a core NAM toolbox and workflow for conducting systemic safety assessments for adult consumers. We also present an approach for evaluating how protective and useful the toolbox and workflow are by benchmarking against historical safety decisions. The toolbox includes physiologically based kinetic (PBK) models to estimate systemic Cmax levels in humans, and 3 bioactivity platforms, comprising high-throughput transcriptomics, a cell stress panel, and in vitro pharmacological profiling, from which points of departure are estimated. A Bayesian model was developed to quantify the uncertainty in the Cmax estimates depending on how the PBK models were parameterized. The feasibility of the evaluation approach was tested using 24 exposure scenarios from 10 chemicals, some of which would be considered high risk from a consumer goods perspective (eg, drugs that are systemically bioactive) and some low risk (eg, existing food or cosmetic ingredients). Using novel protectiveness and utility metrics, it was shown that up to 69% (9/13) of the low risk scenarios could be identified as such using the toolbox, whilst being protective against all (5/5) the high-risk ones. The results demonstrated how robust safety decisions could be made without using animal data. This work will enable a full evaluation to assess how protective and useful the toolbox and workflow are across a broader range of chemical-exposure scenarios.
Indexed as
Identifiers
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.