Publication Details |
| Category | Text Publication |
| Reference Category | Journals |
| DOI | 10.1016/j.envint.2026.110465 |
Licence  |
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| Title (Primary) | Mapping disease-linked AOPs to inform bioassay selection for chemical hazard assessment |
| Author | Stevens, S.; Muncke, J.; Escher, B.I.
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| Source Titel | Environment International |
| Year | 2026 |
| Department | ZELLTOX |
| Volume | 215 |
| Page From | art. 110465 |
| Language | englisch |
| Topic | T9 Healthy Planet |
| Data and Software links | https://doi.org/10.5281/zenodo.20137237 |
| Supplements | Supplement 1 Supplement 2 |
| Keywords | In vitro bioassay; New approach methodology (NAM); Effect assessment; Key characteristics of toxicants; Adverse outcome pathways (AOP) |
| Abstract | Modern
societies synthesize, distribute, and utilize thousands of chemicals,
but their contribution to the global burden of non-communicable diseases
remains insufficiently characterized. Improved availability of robust
hazard data would enable more systematic assessment, prioritization, and
management of chemical-related health risks. New Approach Methodologies
(NAM) are promising because they provide high-throughput,
mechanistically informative, and animal-free testing that improves
current regulatory toxicity testing. However, selecting biologically
relevant in-vitro assays capable of predicting chemical-induced effects
remains a challenge. Here, we present a systematic strategy for
assembling relevant in-vitro assays. We identified critical molecular
and cellular key events of Adverse Outcome Pathways (AOPs) across six
clusters of diseases that can be triggered by chemical exposure.
Curation and filtering of 487 AOPs resulted in 266 AOPs, which were
manually mapped to the AOP networks of disease clusters containing 25–84
AOPs each. The three most frequently occurring key events across all
clusters were cytotoxicity (6/6 clusters), oxidative stress (5/6
clusters), and mitochondrial dysfunction (4/6 clusters). This
prioritization aligns with oxidative stress as an overarching “key
characteristic of toxicants”. Receptor-mediated key events were also
frequent, with aryl hydrocarbon and estrogen receptor activation in
multiple clusters. Other key events were cluster-specific, such as
triglyceride accumulation in metabolic diseases. Building on this
analysis, we propose high-throughput cell-based assays covering critical
endpoints by integrating the key characteristics of toxicants framework
to ensure coverage beyond current AOP limitations. A panel of 15
multiplexed assays meeting criteria for simplicity, robustness, and
high-throughput could enable efficient screening of single chemicals or
chemical mixtures. |
| Stevens, S., Muncke, J., Escher, B.I. (2026): Mapping disease-linked AOPs to inform bioassay selection for chemical hazard assessment Environ. Int. 215 , art. 110465 10.1016/j.envint.2026.110465 |
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