Evidence map›Paper›PMID 39826153›Full record

ArticleALTEX2025

Mapping out strategies to further develop human-relevant, new approach methodology (NAM)-based developmental neurotoxicity (DNT) testing.

Eike Cöllen, Kristina Bartmann, Jonathan Blum, Kelly Carstens, Ivana Celardo, Nivedita Chatterjee, Marco Corvaro, Nadine Dreser, Ellen Fritsche, Thomas Hartung and 18 more

Abstract read
In one paragraph

Article in ALTEX, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

28 authors.

Eike CöllenIn vitro toxicology and biomedicine, inaugurated by the Doerenkamp-Zbinden foundation, University of Konstanz, Konstanz, Germany.
Kristina BartmannDNTOX GmbH, Düsseldorf, Germany.
Jonathan BlumIn vitro toxicology and biomedicine, inaugurated by the Doerenkamp-Zbinden foundation, University of Konstanz, Konstanz, Germany.
Kelly CarstensCenter for Computational Toxicology and Exposure, Office of Research and Development, United States Environmental Protection Agency, Research Triangle Park, NC, USA.
Ivana CelardoIn vitro toxicology and biomedicine, inaugurated by the Doerenkamp-Zbinden foundation, University of Konstanz, Konstanz, Germany.
Nivedita ChatterjeeNanoSafety Group, International Iberian Nanotechnology Laboratory, Braga, Portugal.
Marco CorvaroCorteva Agriscience Italia, S.r.l., Rome, Italy.
Nadine DreserIn vitro toxicology and biomedicine, inaugurated by the Doerenkamp-Zbinden foundation, University of Konstanz, Konstanz, Germany.
Ellen FritscheDNTOX GmbH, Düsseldorf, Germany.
Thomas HartungCenter for Alternatives to Animal Testing, Department of Environmental Health and Engineering, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Helena T HogbergNational Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods, Division of Translational Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
Thomas KnudsenUS EPA Center for Computational Toxicology and Exposure, Research Triangle Park, NC, USA (retired).
Katharina KochDNTOX GmbH, Düsseldorf, Germany.
Anna KreutzInotiv, Morrisville, NC, USA.
Malene LislienDepartment of Chemical Toxicology, Norwegian Institute of Public Health, Oslo, Norway.
Viktoria MagelIn vitro toxicology and biomedicine, inaugurated by the Doerenkamp-Zbinden foundation, University of Konstanz, Konstanz, Germany.
M Sue MartyDow Chemical Company, Midland, MI, USA.
Giorgia PalloccaIn vitro toxicology and biomedicine, inaugurated by the Doerenkamp-Zbinden foundation, University of Konstanz, Konstanz, Germany.
Anna Bal-PriceEuropean Commission Joint Research Centre, Ispra, Italy.
Costanza RovidaCAAT-Europe, University of Konstanz, Konstanz, Germany.
Magdalini SachanaEnvironment Health and Safety Division, Environment Directorate, Organisation for Economic Cooperation and Development (OECD), Paris, France.
Timothy J ShaferCenter for Computational Toxicology and Exposure, Office of Research and Development, United States Environmental Protection Agency, Research Triangle Park, NC, USA.
Lena SmirnovaCenter for Alternatives to Animal Testing, Department of Environmental Health and Engineering, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Ilinca SuciuIn vitro toxicology and biomedicine, inaugurated by the Doerenkamp-Zbinden foundation, University of Konstanz, Konstanz, Germany.
Yaroslav TanaskovIn vitro toxicology and biomedicine, inaugurated by the Doerenkamp-Zbinden foundation, University of Konstanz, Konstanz, Germany.
Silvia TangianuIn vitro toxicology and biomedicine, inaugurated by the Doerenkamp-Zbinden foundation, University of Konstanz, Konstanz, Germany.
Chiara WolfbeiszIn vitro toxicology and biomedicine, inaugurated by the Doerenkamp-Zbinden foundation, University of Konstanz, Konstanz, Germany.
Marcel LeistIn vitro toxicology and biomedicine, inaugurated by the Doerenkamp-Zbinden foundation, University of Konstanz, Konstanz, Germany.

Funding

Pilot Project ProgramP30ES032756 · NIEHS · JOHNS HOPKINS UNIVERSITY · PI Marsha Wills-Karp · 2022 to 2026
$6.0M
Neurotoxicity due to Environmental complex Metal Mixtures ExposureRF1NS130672 · NINDS · JOHNS HOPKINS UNIVERSITY · PI BISWAL, SHYAM, HARTUNG, THOMAS · 2022 to 2022
$2.4M
Neurotoxicity due to Environmental complex Metal Mixtures ExposureR01NS130672 · NINDS · JOHNS HOPKINS UNIVERSITY · PI Shyam Biswal, Thomas Hartung · 2025 to 2026
$1.5M
FDA HHS U01 FD004230Intramural NIH HHS Z99 ES999999NIEHS NIH HHS P30 ES032756NIH HHS HHSN273201500010CNINDS NIH HHS R01 NS130672NINDS NIH HHS RF1 NS130672
6 · The paper itself

Abstract

On occasion of the DNT5 meeting in Konstanz, Germany (April 2024), participants brainstormed on future challenges concerning a regulatory implementation of the developmental neurotoxicity (DNT) in vitro test battery (DNT-IVB). The five discussion topics below outline some of the key issues, opportunities, and research directions for the next several years: (1) How to contextualize DNT hazard with information on potential maternal toxicity or other toxicity domains (non-DNT)? Several approaches on how to use cytotoxicity data from new approach methodologies (NAMs) were dis­cussed. (2) What opportunities exist for an immediate or near-future application of the DNT-IVB, e.g., as a prioritization step or add-on to other information? Initial examples are already emerging; the data can be used even if the battery is not converted to a defined approach. (3) How to establish data interpretation procedures for multi-dimensional endpoints that reduce dimensionality and are suitable for classification? A decision framework is required on how to use the DNT-IVB in a regu­latory context. Machine learning may provide novel classification models. (4) How can a battery of molecular initiating events (MIEs) be smartly linked to the DNT-IVB? At what tier of an overall strategy would MIEs be evaluated, and how would one optimally balance cost vs information yield. (5) What is the way forward to scientific validation of DNT NAMs and the DNT-IVB? A large set of animal data would be required for conventional approaches, while mechanistic information may establish relevance in other ways.

Indexed as

Animal Testing AlternativesNeurotoxicity SyndromesToxicity TestsAnimalsHumansadverse outcome pathways (AOP)cytotoxicity, screeningDNT in vitro test battery (DNT-IVB)key neurodevelopmental processes (KNDP)new approach methodologies (NAMs)next generation risk assessement (NGRA)physiologically-based kinetic modelling (PBK

Identifiers

PMID39826153
PMCPMC13504761

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.