Novel Methods and Applications in Zebrafish as a Model for Mixture Toxicity

A Special Issue of Toxics (ISSN 2305-6304) belonging to the section "Novel Methods in Toxicology Research".

Deadline for manuscript submissions: 1 December 2026 | Viewed by 518

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Department of Environmental and Molecular Toxicology, Sinnhuber Aquatic Research Laboratory, Oregon State University, Corvallis, OR 97333, USA
Interests: computational toxicology; developmental toxicity; zebrafish; high-throughput screening; new approach methods (NAMs)
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Special Issue Information

Dear Colleagues,

Chemical risk assessment has long relied on single-compound testing paradigms, yet real-world exposures are inherently complex—involving simultaneous exposure to multiple chemicals across diverse environmental, occupational, and consumer contexts. This disconnect between laboratory practice and biological reality underscores an urgent need for models and methods capable of capturing the complexity of mixture toxicity.

This Special Issue highlights zebrafish (Danio rerio) as a powerful and versatile platform for advancing mixture toxicity research. As a well-established New Approach Methodology (NAM), zebrafish offer a unique combination of biological complexity, high-throughput compatibility, and translational relevance that makes them ideally suited for studying the additive, synergistic, and antagonistic effects that characterize real-world chemical exposures.

Contributions to this collection will showcase novel methodological approaches and emerging applications—spanning automated phenotypic screening, computational modeling, multi-omics integration, and behavioral analysis—that expand the toolkit available for mixture toxicity evaluation. By bringing together researchers using a common model organism, this Special Issue seeks to foster cross-laboratory learning and methodological harmonization.

Ultimately, this collection aims to accelerate the development of robust, biologically informed frameworks for mixture risk assessment and support the broader transition toward next-generation toxicology.

Dr. Lisa Truong
Guest Editor

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Keywords

  • zebrafish
  • chemical mixture toxicity
  • environmental mixture exposures
  • synergism, antagonism, and additivity
  • new approach methodologies (NAMs)

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Published Papers (1 paper)

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Research

23 pages, 2736 KB  
Article
aip Mutant Zebrafish Display Morphological and Transcriptional Changes Associated with Stress-Induced Hematopoiesis
by Spencer R. Stinson, Jane K. La Du, Dante M. Perone, Sibel I. Karchner, Neelakanteswar Aluru, Lisa Truong, Mark E. Hahn and Robyn L. Tanguay
Toxics 2026, 14(9), 807; https://doi.org/10.3390/toxics14090807 - 11 Sep 2026
Abstract
The Aryl Hydrocarbon Receptor (AHR) is a versatile receptor that binds various compounds, triggering downstream transcriptional changes involved in the regulation of xenobiotic metabolism and cell fate. The Ahr Interacting Protein (AIP), also known as XAP2 and ARA9, is a molecular chaperone essential [...] Read more.
The Aryl Hydrocarbon Receptor (AHR) is a versatile receptor that binds various compounds, triggering downstream transcriptional changes involved in the regulation of xenobiotic metabolism and cell fate. The Ahr Interacting Protein (AIP), also known as XAP2 and ARA9, is a molecular chaperone essential for the cytosolic retention and stabilization of the AHR. Past studies, and AIP-linked human pathologies, suggest an alternative developmental role of the AIP apart from the AHR and canonical xenobiotic response. A null mutation of the AIP in zebrafish larvae (designated as aipwh86) resulted in craniofacial malformations, failure to inflate the swim bladder, and an enlarged and darkened liver, emerging at 5–6 days post-fertilization (dpf). Histopathological analysis at 5 dpf suggested no histological differences in the homozygous (HMZ) mutant compared to the wild type (WT). Whole-larvae RNA sequencing at 6 and 7 dpf showed significant dysregulation of key transcripts in the mutant larvae compared to WT, with pathway analysis revealing alterations in embryonic hematopoiesis and cardiac development. RT-qPCR validation showed that transcripts involved in the Hif-mediated pathway were overexpressed as early as 5 dpf. O-dianisidine staining at 6 dpf showed an increase in hemoglobin within the liver and cardiac regions of the mutant AIP larvae. This study demonstrates the complex and diverse role of AIP in vertebrate embryonic development and physiology. Full article
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