Details zur Publikation |
| Kategorie | Textpublikation |
| Referenztyp | Zeitschriften |
| DOI | 10.1016/j.envint.2026.110413 |
Lizenz  |
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| Titel (primär) | Predicting the immunotoxic potential of chemical mixtures based on their endocrine activity profiles via computational modeling and in vitro bioassays |
| Autor | Braun, G.; Hilscherová, K.; van Brummelen, S.; Pieters, R.; Smutná, M.; Wojtysiak, N.; Escher, B.
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| Quelle | Environment International |
| Erscheinungsjahr | 2026 |
| Department | ZELLTOX |
| Band/Volume | 214 |
| Seite von | art. 110413 |
| Sprache | englisch |
| Topic | T9 Healthy Planet |
| Supplements | Supplement 1 Supplement 2 |
| Keywords | Mixture effects; EDCs; Immunomodulation; In vitro bioassays; Concentration addition |
| Abstract | Exposure
to endocrine disrupting chemicals (EDCs) is a known threat to the
environment and human health, because EDCs can interfere with many
developmental processes. As immune cells rely on signaling pathways than
can be impacted by EDCs, the disruption of endocrine processes exhibits
the potential to directly or indirectly adversely alter immune
response. We employed a high-throughput in silico workflow to
identify EDCs that are likely to alter endocrine and metabolic processes
with direct or indirect immunotoxic potential. Initially included
83,693 chemicals were reduced to a priority list of 6,620 and matched
with blood concentrations as reported in human biomonitoring studies.
Mixtures in representative concentration ratios were prepared for five
main groups of EDCs with five chemicals per mixture, covering per- and
polyfluorinated compounds, halogenated pesticides, phthalates, phenols,
and polycyclic aromatic hydrocarbons, and one mixture containing all 25
chemicals. Single compounds and mixtures were tested in high-throughput
bioassays covering potential indirect modulators of immune response such
as endocrine signaling through activation of estrogen receptor,
androgen receptor, glucocorticoid receptor and aryl hydrocarbon
receptor, thyroid hormone signaling through agonism and antagonism on
the thyroid hormone receptor, thyroperoxidase inhibition, and
transthyretin binding, or more direct endpoints such as pro-inflammatory
signaling through the activation of nuclear factor
κ-light-chain-enhancer of activated B cells, as well as redox and
metabolic imbalance via oxidative stress response and mitochondrial
disruption. 19 out of 33 bioactive mixtures confirmed concentration
additivity across all tested endpoints within 3-fold deviation,
indicating a clear relevance of commonly detected EDCs mixtures as
potential immunomodulators. |
| Braun, G., Hilscherová, K., van Brummelen, S., Pieters, R., Smutná, M., Wojtysiak, N., Escher, B. (2026): Predicting the immunotoxic potential of chemical mixtures based on their endocrine activity profiles via computational modeling and in vitro bioassays Environ. Int. 214 , art. 110413 10.1016/j.envint.2026.110413 |
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