
Exploring mode-of-action for acute toxicity of primary aromatic amines with D. magna using differential gene expression analysis
- Author
- Friedel Dewulf (UGent) , Ilias Semmouri (UGent) , Filip Van Nieuwerburgh (UGent) , Karel De Schamphelaere (UGent) and Jana Asselman (UGent)
- Organization
- Abstract
- Organic pollutants, with their diverse structures and modes-of-action (MOAs), pose a significant challenge in understanding and predicting their toxic effects on the environment. Chemicals can be grouped according to toxicity in among others nonpolar narcotics, polar narcotics, reactive chemicals, and specifically acting chemicals. Non-polar narcotics (baseline toxicants) act via a non-specific MOA, with their toxicity linked to hydrophobicity. Polar narcotics are slightly more toxic, while reactive and specifically acting chemicals show enhanced toxicity due to more specific MOAs and targets. The MOA of a chemical is also linked with its interspecies variation in toxicity: structurally analogous narcotics typically demonstrate limited interspecies variations in toxicity, while chemicals with a specific or reactive MOA display elevated interspecies variation, primarily attributed to the specific MOA in exceptionally sensitive species. In that respect, aromatic amines exhibit distinctive toxicity characteristics. Although they have been classified as 'polar narcotics', certain substitution patterns of the aromatically bound amino group result in a large interspecies variation in toxicity, due to their excess toxicity towards species such as D. magna. In this context, we investigated three primary aromatic amines (PAAs) in D. magna: 4,4’-MDA, 2,2’-MDA and 2,4-TDA. Despite their structural and chemical similarities, they exert very distinct biological effects. Therefore, we studied their MOA by acute exposure experiments in the model organism D. magna to study its gene expression in response to PAA exposure. Our experimental design also included two reference compounds, a non-polar narcotic (1-octanol) and aniline. Our analysis showed, both in terms of acute immobility and gene expression patterns, very distinct biological MOAs for the three PAAs. While 4,4’-MDA treatment showed similar effects as aniline, its isomer 2,2’-MDA showed similar effects as 1-octanol. 2,4-TDA had an EC10 value in between the other two PAAs and did not induce any differential gene expression compared to the negative control at its EC10 concentration. These results indicate towards a specific influence of substituent positioning in PAAs on their toxicity and MOA towards D. magna.
- Keywords
- Daphnia magna, Primary aromatic amines, Ecotoxicity, Transcriptomics, Mode of action
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Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-01HXS29NVC640NJVAAZTEFB41A
- MLA
- Dewulf, Friedel, et al. “Exploring Mode-of-Action for Acute Toxicity of Primary Aromatic Amines with D. Magna Using Differential Gene Expression Analysis.” SETAC Europe, 34th Annual Meeting, Abstracts, 2024, pp. 115–16.
- APA
- Dewulf, F., Semmouri, I., Van Nieuwerburgh, F., De Schamphelaere, K., & Asselman, J. (2024). Exploring mode-of-action for acute toxicity of primary aromatic amines with D. magna using differential gene expression analysis. SETAC Europe, 34th Annual Meeting, Abstracts, 115–116.
- Chicago author-date
- Dewulf, Friedel, Ilias Semmouri, Filip Van Nieuwerburgh, Karel De Schamphelaere, and Jana Asselman. 2024. “Exploring Mode-of-Action for Acute Toxicity of Primary Aromatic Amines with D. Magna Using Differential Gene Expression Analysis.” In SETAC Europe, 34th Annual Meeting, Abstracts, 115–16.
- Chicago author-date (all authors)
- Dewulf, Friedel, Ilias Semmouri, Filip Van Nieuwerburgh, Karel De Schamphelaere, and Jana Asselman. 2024. “Exploring Mode-of-Action for Acute Toxicity of Primary Aromatic Amines with D. Magna Using Differential Gene Expression Analysis.” In SETAC Europe, 34th Annual Meeting, Abstracts, 115–116.
- Vancouver
- 1.Dewulf F, Semmouri I, Van Nieuwerburgh F, De Schamphelaere K, Asselman J. Exploring mode-of-action for acute toxicity of primary aromatic amines with D. magna using differential gene expression analysis. In: SETAC Europe, 34th Annual Meeting, Abstracts. 2024. p. 115–6.
- IEEE
- [1]F. Dewulf, I. Semmouri, F. Van Nieuwerburgh, K. De Schamphelaere, and J. Asselman, “Exploring mode-of-action for acute toxicity of primary aromatic amines with D. magna using differential gene expression analysis,” in SETAC Europe, 34th Annual Meeting, Abstracts, Sevilla, Spain, 2024, pp. 115–116.
@inproceedings{01HXS29NVC640NJVAAZTEFB41A, abstract = {{Organic pollutants, with their diverse structures and modes-of-action (MOAs), pose a significant challenge in understanding and predicting their toxic effects on the environment. Chemicals can be grouped according to toxicity in among others nonpolar narcotics, polar narcotics, reactive chemicals, and specifically acting chemicals. Non-polar narcotics (baseline toxicants) act via a non-specific MOA, with their toxicity linked to hydrophobicity. Polar narcotics are slightly more toxic, while reactive and specifically acting chemicals show enhanced toxicity due to more specific MOAs and targets. The MOA of a chemical is also linked with its interspecies variation in toxicity: structurally analogous narcotics typically demonstrate limited interspecies variations in toxicity, while chemicals with a specific or reactive MOA display elevated interspecies variation, primarily attributed to the specific MOA in exceptionally sensitive species. In that respect, aromatic amines exhibit distinctive toxicity characteristics. Although they have been classified as 'polar narcotics', certain substitution patterns of the aromatically bound amino group result in a large interspecies variation in toxicity, due to their excess toxicity towards species such as D. magna. In this context, we investigated three primary aromatic amines (PAAs) in D. magna: 4,4’-MDA, 2,2’-MDA and 2,4-TDA. Despite their structural and chemical similarities, they exert very distinct biological effects. Therefore, we studied their MOA by acute exposure experiments in the model organism D. magna to study its gene expression in response to PAA exposure. Our experimental design also included two reference compounds, a non-polar narcotic (1-octanol) and aniline. Our analysis showed, both in terms of acute immobility and gene expression patterns, very distinct biological MOAs for the three PAAs. While 4,4’-MDA treatment showed similar effects as aniline, its isomer 2,2’-MDA showed similar effects as 1-octanol. 2,4-TDA had an EC10 value in between the other two PAAs and did not induce any differential gene expression compared to the negative control at its EC10 concentration. These results indicate towards a specific influence of substituent positioning in PAAs on their toxicity and MOA towards D. magna.}}, author = {{Dewulf, Friedel and Semmouri, Ilias and Van Nieuwerburgh, Filip and De Schamphelaere, Karel and Asselman, Jana}}, booktitle = {{SETAC Europe, 34th Annual Meeting, Abstracts}}, issn = {{2309-8031}}, keywords = {{Daphnia magna,Primary aromatic amines,Ecotoxicity,Transcriptomics,Mode of action}}, language = {{eng}}, location = {{Sevilla, Spain}}, pages = {{115--116}}, title = {{Exploring mode-of-action for acute toxicity of primary aromatic amines with D. magna using differential gene expression analysis}}, year = {{2024}}, }