PUBLICATION
The effects of aliphatic alcohols and related acid metabolites in zebrafish embryos - correlations with rat developmental toxicity and with effects in advanced life stages in fish
- Authors
- van der Ven, L.T.M., Schoonen, W.G., Groot, R.M., den Ouden, F., Heusinkveld, H.J., Zwart, E.P., Hodemaekers, H.M., Rorije, E., de Knecht, J.
- ID
- ZDB-PUB-201002-174
- Date
- 2020
- Source
- Toxicology and applied pharmacology 407: 115249 (Journal)
- Registered Authors
- Heusinkveld, Harm, van der Ven, Leo
- Keywords
- Adverse outcome pathways, Alkoxy alcohols, Developmental toxicity, Metabolism, Zebrafish embryos
- MeSH Terms
-
- Animals
- Carboxylic Acids/toxicity*
- Embryo, Nonmammalian/metabolism*
- Embryonic Development/drug effects
- Ethanol/toxicity
- Fatty Alcohols/toxicity*
- Female
- Gene Expression Regulation, Developmental/drug effects
- Hexanols/toxicity
- Lethal Dose 50
- Pregnancy
- Rats
- Toxicity Tests
- Water Pollutants, Chemical/toxicity
- Zebrafish/growth & development
- Zebrafish/metabolism*
- PubMed
- 32979392 Full text @ Tox. App. Pharmacol.
- CTD
- 32979392
Citation
van der Ven, L.T.M., Schoonen, W.G., Groot, R.M., den Ouden, F., Heusinkveld, H.J., Zwart, E.P., Hodemaekers, H.M., Rorije, E., de Knecht, J. (2020) The effects of aliphatic alcohols and related acid metabolites in zebrafish embryos - correlations with rat developmental toxicity and with effects in advanced life stages in fish. Toxicology and applied pharmacology. 407:115249.
Abstract
The zebrafish embryo toxicity test (ZFET) is a simple medium-throughput test to inform about (sub)acute lethal effects in embryos. Enhanced analysis through morphological and teratological scoring, and through gene expression analysis, detects developmental effects and the underlying toxicological pathways. Altogether, the ZFET may inform about hazard of chemical exposure for embryonal development in humans, as well as for lethal effects in juvenile and adult fish. In this study, we compared the effects within a series of 12 aliphatic alcohols and related carboxylic acid derivatives (ethanol, acetic acid, 2-methoxyethanol, 2-methoxyacetic acid, 2-butoxyethanol, 2-butoxyacetic acid, 2-hydroxyacetic acid, 2-ethylhexan-1-ol, 2-ethylhexanoic acid, valproic acid, 2-aminoethanol, 2-(2-hydroxyethylamino)ethanol) in ZFET and early life stage (ELS, 28d) exposures, and compared ZFET results with existing results of rat developmental studies and LC50s in adult fish. High correlation scores were observed between compound potencies in ZFET with either ELS, LC50 in fish and developmental toxicity in rats, indicating similar potency ranking among the models. Compounds could be mapped to specific pathways in an adverse outcome pathway (AOP) network through morphological scoring and gene expression analysis in ZFET. Similarity of morphological effects and gene expression profiles in pairs of alcohols with their acid metabolites suggested metabolic activation of the parent alcohols, although with additional, metabolite-independent activity independent for ethanol and 2-ethylhexanol. Overall, phenotypical and gene expression analysis with these compounds indicates that the ZFET can potentially contribute to the AOP for developmental effects in rodents, and to predict toxicity of acute and chronic exposure in advanced life stages in fish.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping