Implications of the solvent vehicles dimethylformamide and dimethylsulfoxide for establishing transcriptomic endpoints in the zebrafish embryo toxicity test
Abstract
Current aquatic chemical testing guidelines recognize that solvents can potentially interfere with the organism or environmental conditions of aquatic ecotoxicity tests and therefore recommend concentration limits for their use. These recommendations are based on evidence of adverse solvent effects in apical level tests. The growing importance of subapical and chronic endpoints in future test strategies, however, suggests that the limits may need reassessment. To address this concern, microarrays were used to determine the effects of organic solvents, dimethylformamide (DMF) and dimethylsulfoxide (DMSO), on the transcriptome of zebrafish (Danio rerio) embryos. Embryos were exposed for 48 h to a range of concentrations between 0.025 and 32.0 ml/L. Effects on survival and development after 24 and 48 h were assessed microscopically, with no effects on mortality or morphology up to 2.0 and 16.0 ml/L for DMF and DMSO. However, analysis of 48-h embryonic RNA revealed large numbers of differentially expressed genes at concentrations well below the 0.1 ml/L solvent limit level. The enrichment of differentially expressed genes was found for metabolic, developmental, and other key biological processes, some of which could be linked to observed morphological effects at higher solvent concentrations. These findings emphasize the need to remove or lower as far as possible the concentrations of solvent carriers in ecotoxicology tests.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
DMSO, used here as the carrier solvent for DEHP, may be a contributing factor to the elevated ingestion of PEST + DEHP.
“DMSO, used here as the carrier solvent (Brayton, 1986; Turner et al., 2012) for DEHP, may be a contributing factor.”
From Trophic transfer of polyester microfibres across a multi-level marine food web. (2025) · cites this paper as Turner et al., 2012
Cites
Gene Ontology: tool for the unification of biology
Ashburner, M., Ball, C. A., Blake, J. A., Botstein, D., Butler, H., Cherry, J. M., Davis, A. P., Dolinski, K., Dwight, S. S., Eppig, J. T., et al. (2000) · Nature Genetics · doi:10.1038/75556 · Cited by 43,206 · see citing works
Statistical significance for genomewide studies
Storey, J. D., & Tibshirani, R. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1530509100 · Cited by 9,692 · see citing works
International Organization for Standardization
Gargaud, M., Irvine, W. M., Amils, R., Pinti, D. L., Cernicharo, J., Rouan, D., Spohn, T., Tirard, S., & Viso, M. (2015) · Encyclopedia of Astrobiology · doi:10.1007/978-3-662-44185-5_100574 · Cited by 6,716 · see citing works
limma: Linear Models for Microarray Data
Smyth, G. K. (2005) · Statistics for Biology and Health · doi:10.1007/0-387-29362-0_23 · Cited by 5,796 · see citing works
KAAS: an automatic genome annotation and pathway reconstruction server
Moriya, Y., Itoh, M., Okuda, S., Yoshizawa, A. C., & Kanehisa, M. I. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm321 · Cited by 4,128 · see citing works
Ankley, G. T., Bennett, R. S., Erickson, R. J., Hoff, D. J., Hornung, M. W., Johnson, R. D., Mount, D. R., Nichols, J. W., Russom, C. L., Schmieder, P. K., et al. (2009) · Environmental Toxicology and Chemistry · doi:10.1002/etc.34 · Cited by 2,734 · see citing works
(2002) · doi:10.1093/oso/9780199638086.001.0001 · Cited by 589 · see citing works
Normalization for cDNA microarry data
Yang, J. Y. H., Dudoit, S., Luu, P., & Speed, T. P. (2001) · Proceedings of SPIE, the International Society for Optical Engineering/Proceedings of SPIE · doi:10.1117/12.427982 · Cited by 442 · see citing works
Braunbeck, T. A., Boettcher, M. I., Hollert, H., et al. (2005) · PubMed · Cited by 364 · see citing works
Toxicogenomics in Regulatory Ecotoxicology
Ankley, G. T., Daston, G. P., Degitz, S. J., et al. (2006) · Environmental Science & Technology · doi:10.1021/es0630184 · Cited by 279 · see citing works
Acute and chronic effects of carrier solvents in aquatic organisms: A critical review
Hutchinson, T. H., Shillabeer, N., Winter, M. J., et al. (2005) · Aquatic Toxicology · doi:10.1016/j.aquatox.2005.09.008 · Cited by 275 · see citing works
Henry, T. B., Menn, F., Fleming, J. T., Wilgus, J. R., Compton, R. N., & Sayler, G. S. (2007) · Environmental Health Perspectives · doi:10.1289/ehp.9757 · Cited by 257 · see citing works
Hallare, A. V., Köhler, H., & Triebskorn, R. A. (2004) · Chemosphere · doi:10.1016/j.chemosphere.2004.04.007 · Cited by 246 · see citing works
Hallare, A. V., Nagel, K., Köhler, H., et al. (2005) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2005.07.006 · Cited by 244 · see citing works
Molecular Networks: The Top-Down View
Bray, D. (2003) · Science · doi:10.1126/science.1089118 · Cited by 214 · see citing works
Transcriptional profiling reveals barcode-like toxicogenomic responses in the zebrafish embryo
Yang, L., Kemadjou, J. R., Zinsmeister, C., Bauer, M. F., Legradi, J., Müller, F., Pankratz, M. J., Jäkel, J., & Strähle, U. (2007) · Genome biology · doi:10.1186/gb-2007-8-10-r227 · Cited by 190 · see citing works
Vision & strategy: Predictive ecotoxicology in the 21st century
Villeneuve, D. L., & García‐Reyero, N. (2010) · Environmental Toxicology and Chemistry · doi:10.1002/etc.396 · Cited by 171 · see citing works
van Aggelen, G. C., Ankley, G. T., Baldwin, W. S., Bearden, D. W., Benson, W. H., Chipman, J. K., Collette, T. W., Craft, J. A., Denslow, N. D., Embry, M. R., et al. (2009) · Environmental Health Perspectives · doi:10.1289/ehp.0900985 · Cited by 170 · see citing works
Heckmann, L., Sibly, R. M., Connon, R. E., Hooper, H. L., Hutchinson, T. H., Maund, S., Hill, C. J., Bouétard, A., & Callaghan, A. (2008) · Genome biology · doi:10.1186/gb-2008-9-2-r40 · Cited by 168 · see citing works
Acute effects of diclofenac and DMSO to Daphnia magna: Immobilisation and hsp70-induction
Haap, T., Triebskorn, R. A., & Köhler, H. (2008) · Chemosphere · doi:10.1016/j.chemosphere.2008.05.062 · Cited by 147 · see citing works
Biological impacts and context of network theory
Almaas, E. (2007) · Journal of Experimental Biology · doi:10.1242/jeb.003731 · Cited by 131 · see citing works
van den Hurk, R., & Slof, G. A. (1981) · Cell and Tissue Research · doi:10.1007/bf00210109 · Cited by 93 · see citing works
Wit, M. D., Keil, D., van der Ven, K., Vandamme, S., Witters, E., & Coen, W. D. (2010) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2010.03.003 · Cited by 90 · see citing works
Rufli, H., Fisk, P. R., Girling, A. E., et al. (1998) · Ecotoxicology and Environmental Safety · doi:10.1006/eesa.1997.1612 · Cited by 62 · see citing works
Transcriptomics and proteomics. Applications to ecotoxicology
Calzolai, L., Ansorge, W. J., Calabrese, E. J., et al. (2007) · Comparative Biochemistry and Physiology Part D Genomics and Proteomics · doi:10.1016/j.cbd.2007.04.007 · Cited by 46 · see citing works
Sawle, A., Wit, E. C., Whale, G., et al. (2010) · Toxicological Sciences · doi:10.1093/toxsci/kfq237 · Cited by 39 · see citing works
Self-citationWang, R., Biales, A. D., Bencic, D. C., et al. (2008) · Environmental Toxicology and Chemistry · doi:10.1897/07-191.1 · Cited by 35 · see citing works
Mortensen, A. S., & Arukwe, A. (2006) · Aquatic Toxicology · doi:10.1016/j.aquatox.2006.05.009 · Cited by 33 · see citing works
Dimethyl formamide (DMFA) and ethylene glycol (EG) are estrogenic in rainbow trout
Ren, L., Meldahl, A., & Lech, J. J. (1996) · Chemico-Biological Interactions · doi:10.1016/0009-2797(96)03727-1 · Cited by 27 · see citing works
Gene Expression Dose-Response of Liver with a Genotoxic and Nongenotoxic Carcinogen
Seidel, S. D., Stott, W. T., Kan, H. L., Sparrow, B., & Gollapudi, B. B. (2006) · International Journal of Toxicology · doi:10.1080/10915810500488429 · Cited by 15 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Gaballah, S., Swank, A., Sobus, J. R., Howey, X. M., Schmid, J., Catron, T., McCord, J., Hines, E., Strynar, M., & Tal, T. (2020) · Environmental Health Perspectives · doi:10.1289/ehp5843 · Cited by 437 · see citing works
Trophic transfer of polyester microfibres across a multi-level marine food web.
Miller, M. E., Motti, C. A., Snekkevik, V. K., Vickers, K., Kennedy, H., Bastin, L., Hamann, M., & Kroon, F. J. (2025) · Marine Pollution Bulletin · doi:10.1016/j.marpolbul.2025.118590 · Cited by 9 · see citing works
- Authors
- Turner, C., Sawle, A., Fenske, M., & Cossins, A.
- Affiliations
- University of Liverpool (GB)
- Fraunhofer Institute for Molecular Biology and Applied Ecology (DE)
- Corresponding author
- Fenske, Martina
- Venue
- Environmental Toxicology and Chemistry
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-12-14
- Volume
- 31
- Issue
- 3
- Pages
- 593-604
- ISSN
- 0730-7268 (ISSN-L)
- 1552-8618
- OpenAlex
- W2070012859
- Cited by
- 39
- References
- 30
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 3 · 2023: 2 · 2021: 2 · 2020: 5 · 2019: 3 · 2018: 2 · 2017: 1 · 2016: 3 · 2015: 3 · 2014: 3 · 2013: 3 · 2012: 2
- FWCI
- 1.85
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Environmental Toxicology and Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Fraunhofer-Publica (Fraunhofer-Gesellschaft) (submittedVersion)
- RWTH Publications (RWTH Aachen) (submittedVersion)
- Funders
- National Centre for the Replacement, Refinement and Reduction of Animals in Research (G0800702/1)
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Environmental Toxicology and Ecotoxicology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Zebrafish Biomedical Research Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Reproductive biology and impacts on aquatic species
- Keywords
- dimethylformamide, dimethyl sulfoxide, organic solvents, transcriptomics, differentially expressed genes, embryonic development, microarray gene expression, aquatic ecotoxicology
- MeSH terms
- Animals, Dimethyl Sulfoxide, Dimethylformamide, Embryo, Nonmammalian, Environmental Monitoring, Solvents, Water Pollutants, Chemical, Zebrafish, Toxicity Tests, Ecotoxicology, Transcriptome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
