ArticleEnvironmental health perspectives2022
Dose Addition in the Induction of Craniofacial Malformations in Zebrafish Embryos Exposed to a Complex Mixture of Food-Relevant Chemicals with Dissimilar Modes of Action.
Article in Environmental health perspectives, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 32 citations in OpenAlex.
- Relevance of kinetic interactions and co-formulants for plant protection product liver toxicity in vitro.Archives of toxicology · 2025Article
- The use of canonical dose-response models for benchmark dose analysis of continuous toxicological data.Critical reviews in toxicology · 2025Review
- A computational dynamic systems model forCurrent research in toxicology · 2025Article
- Basic concepts of mixture toxicity and relevance for risk evaluation and regulation.Archives of toxicology · 2023Article
- Dose additive maternal and offspring effects of oral maternal exposure to a mixture of three PFAS (HFPO-DA, NBP2, PFOS) during pregnancy in the Sprague-Dawley rat.The Science of the total environment · 2023Article
- Determination of in vitro hepatotoxic potencies of a series of perfluoroalkyl substances (PFASs) based on gene expression changes in HepaRG liver cells.Archives of toxicology · 2023Article
- Human risk associated with exposure to mixtures of antiandrogenic chemicals evaluated using in vitro hazard and human biomonitoring data.Environment international · 2023Article
- Application of AOPs to assist regulatory assessment of chemical risks - Case studies, needs and recommendations.Environmental research · 2023Review
- New approach methodologies to facilitate and improve the hazard assessment of non-genotoxic carcinogens-a PARC project.Frontiers in toxicology · 2023Review
- Trichloroethylene: An Invisible Cause of Parkinson's Disease?Journal of Parkinson's disease · 2023Review
- Cumulative maternal and neonatal effects of combined exposure to a mixture of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) during pregnancy in the Sprague-Dawley rat.Environment international · 2022Article
- Retrospective cumulative dietary risk assessment of craniofacial alterations by residues of pesticides.EFSA journal. European Food Safety Authority · 2022Article
- Invited Perspective: How Relevant Are Mode-of-Action Considerations for the Assessment and Prediction of Mixture Effects?Environmental health perspectives · 2022Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHumans are exposed to combinations of chemicals. In cumulative risk assessment (CRA), regulatory bodies such as the European Food Safety Authority consider dose addition as a default and sufficiently conservative approach. The principle of dose addition was confirmed previously for inducing craniofacial malformations in zebrafish embryos in binary mixtures of chemicals with either similar or dissimilar modes of action (MOAs).
objectivesIn this study, we explored a workflow to select and experimentally test multiple compounds as a complex mixture with each of the compounds at or below its no observed adverse effect level (NOAEL), in the same zebrafish embryo model.
methodsSelection of candidate compounds that potentially induce craniofacial malformations was done using
resultsA final selection of eight compounds was examined in the zebrafish embryo model, and craniofacial malformations were observed in embryos exposed to each of the compounds, thus confirming the developmental toxicity as predicted by the DISCUSSION: This case study of a complex mixture inducing craniofacial malformations in zebrafish embryos shows that dose addition can adequately predicted the cumulative effect of a mixture of multiple substances at low doses, irrespective of the (expected) MOA. The applied workflow may be useful as an approach for CRA in general. https://doi.org/10.1289/EHP9888.
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