PUBLICATION
QSAR for baseline toxicity and classification of specific modes of action of ionizable organic chemicals in the zebrafish embryo toxicity test
- Authors
- Klüver, N., Bittermann, K., Escher, B.I.
- ID
- ZDB-PUB-181218-7
- Date
- 2018
- Source
- Aquatic toxicology (Amsterdam, Netherlands) 207: 110-119 (Journal)
- Registered Authors
- Klüver, Nils
- Keywords
- Baseline toxicity QSAR, Danio rerio, Fish embryo toxicity, Ionizable chemicals, Zebrafish
- MeSH Terms
-
- Animals
- Embryo, Nonmammalian/drug effects*
- Inhibitory Concentration 50
- Ions
- Organic Chemicals/chemistry*
- Organic Chemicals/toxicity*
- Quantitative Structure-Activity Relationship*
- Toxicity Tests, Acute*
- Water Pollutants, Chemical/toxicity
- Zebrafish/embryology*
- PubMed
- 30557756 Full text @ Aquat. Toxicol.
Citation
Klüver, N., Bittermann, K., Escher, B.I. (2018) QSAR for baseline toxicity and classification of specific modes of action of ionizable organic chemicals in the zebrafish embryo toxicity test. Aquatic toxicology (Amsterdam, Netherlands). 207:110-119.
Abstract
The fish embryo toxicity (FET) test with the zebrafish Danio rerio is widely used to assess the acute toxicity of chemicals thereby serving as animal alternative to the acute fish toxicity test. The minimal toxicity of neutral chemicals in the FET can be predicted with a previously published Quantitative Structure-Activity Relationship (QSAR) based on the liposome-water partition coefficient Klipw. Such a QSAR may serve to plan toxicity testing and to evaluate whether an observed effect is caused by a specific mode of action (MoA). The applicability domain of this QSAR was extended to ionizable organic chemicals (IOC) without any modification of slope and intercept simply by replacing the Klipw with the speciation-corrected liposome-water distribution ratio (Dlipw(pH)) as descriptor for the uptake into the embryo. FET LC50 values of IOCs were extracted from an existing FET database and published literature. IOCs were selected that are present concomitantly as neutral and charged, species, i.e., acids with an acidity constant pKa <10 and bases with pKa>5. IOCs were grouped according to their putative MoA of acute aquatic toxicity. The toxic ratios (TR) in the FET were derived by of the experimental FET-LC50 in comparison with the baseline toxicity QSAR. Baseline toxicants were confirmed to align well with the FET baseline toxicity QSAR (TR < 10). Chemicals identified to act as specific or reactive chemicals with the toxic ratio analysis in the FET test (TR > 10) were generally consistent with MoA classification for acute fish toxicity with a few exceptions that were suspected to have had issues with the stability of the pH during testing. One critical aspect for the effect analysis of ionizable chemicals is the pH, since the difference between pH and pKa determines the speciation and thereby the Dlipw(pH).
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping