ArticleComputational toxicology (Amsterdam, Netherlands)2025
A comparative study of biostatistical pipelines for benchmark concentration modeling of
Article in Computational toxicology (Amsterdam, Netherlands), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Zebrafish behavioral assessment as a first-tier whole-organism NAM for developmental neurotoxicity: A multi-laboratory evaluation.Neurotoxicology · 2026Article
- Prioritizing chemicals for developmental neurotoxicity by integrating data from a new approach methods (NAMs) battery covering key cellular events in neurodevelopment.Neurotoxicology · 2026Article
- Functional Mapping of Neurodevelopmental Disease Pathways to Key Neurodevelopmental Processes Represented in the Developmental Neurotoxicity In Vitro Testing Battery.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- From concept to regulation: OECD's role in the development of the DNTFrontiers in toxicology · 2026Review
- Statistical analysis of multi-endpoint phenotypic screening increases sensitivity of planarian neurotoxicity testing.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- In Silico Forensic Toxicology: Is It Feasible?Toxics · 2025Review
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
New approach methods (NAMs) have been prioritized to reduce the use of animals for chemical safety assessment while continuing to protect human health and the environment. A key challenge of generating toxicity data is the implementation of a standardized analysis approach for transparent and reproducible benchmark concentration (BMC) estimation and uncertainty quantification for assay developers, regulators, and other stakeholders. In this study, we compared the bioactivity results of 321 chemical samples from four established BMC analysis pipelines used for evaluation of developmental neurotoxicity (DNT) NAMs data: the ToxCast pipeline (tcpl), CRStats, DNT DIVER (Curvep and Hill pipelines). We found an overall activity hit call concordance of 77.2% and highly correlated BMC estimations (r = 0.92 ± 0.02 SD), demonstrating generally good agreement across pipelines. Discordance appeared to be explained predominantly by noise within the data and borderline activity (activity occuring near the benchmark response level). Evaluation of the BMC confidence intervals indicated that pipeline selection may impact the estimation of the BMC lower bound. Consideration of biphasic models appeared important for capturing biologically-relevant changes in activity in the DNT battery. Lastly, different approaches to compute 'selective' bioactivity (activity below the threshold of cytotoxicity) were compared, identifying the CRstats classification model as more stringent for classifying selective activity. Overall, these findings indicated greater confidence in NAMs bioactivity results and emphasize the importance of understanding strengths and uncertainties of concentration-response modeling pipelines for informing biological interpretation and application decision making.
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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.