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| DOI | Resolve DOI: https://doi.org/10.1016/j.yrtph.2023.105336 |
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| Author | Search for: Morash, Michael G.1ORCID identifier: https://orcid.org/0000-0002-2530-3855; Search for: Kirzinger, Morgan W.1; Search for: Achenbach, J. C.1; Search for: Venkatachalam, Ananda B.1; Search for: Cooper, Joëlle Pinsonnault; Search for: Ratzlaff, Deborah E.; Search for: Woodland, Cindy L. A.; Search for: Ellis, Lee D.1 |
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| Affiliation | - National Research Council of Canada. Aquatic and Crop Resource Development
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| Format | Text, Article |
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| Subject | raloxifene; resorcinol; transcriptomics; RNAseq; zebrafish |
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| Abstract | In Canada, the Canadian Environmental Protection Act (1999) requires human health and environmental risk assessments be conducted for new substances prior to their manufacture or import. While this toxicity data is historically obtained using rodents, in response to the international effort to eliminate animal testing, Health Canada is collaborating with the National Research Council (NRC) of Canada to develop a New Approach Method by refining existing NRC zebrafish models. The embryo/larval zebrafish model evaluates systemic (whole body) general toxicity which is currently unachievable with cell-based testing. The model is strengthened using behavioral, toxicokinetic and transcriptomic responses to assess non-visible indicators of toxicity following chemical exposure at sub-phenotypic concentrations. In this paper, the predictive power of zebrafish transcriptomics is demonstrated using two chemicals; Raloxifene and Resorcinol. Raloxifene exposure produced darkening of the liver and malformation of the nose/mandible, while Resorcinol exposure produced increased locomotor activity. Transcriptomic analysis correlated differentially expressed genes with the phenotypic effects and benchmark dose calculations determined that the transcriptomic Point of Departure (POD) occurred at subphenotypic concentrations. Correlating gene expression with apical (phenotypic) effects strengthens confidence in evaluation of chemical toxicity, thereby demonstrating the significant advancement that the larval zebrafish transcriptomics model represents in chemical risk assessment. |
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| Publication date | 2023-01-13 |
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| Publisher | Elsevier |
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| Language | English |
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| Peer reviewed | Yes |
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| Export citation | Export as RIS |
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| Report a correction | Report a correction (opens in a new tab) |
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| Record identifier | 7e964d46-b61b-48fe-be99-6108ae7d3703 |
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| Record created | 2023-03-13 |
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| Record modified | 2023-03-17 |
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