1. Elemental imaging (LA-ICP-MS) of zebrafish embryos to study the toxicokinetics of the acetylcholinesterase inhibitor naled.
- Author
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Halbach K, Wagner S, Scholz S, Luckenbach T, and Reemtsma T
- Subjects
- Animals, Biomarkers metabolism, Biotransformation, Bromine metabolism, Cholinesterase Inhibitors toxicity, Chromatography, Liquid, Embryo, Nonmammalian drug effects, Embryo, Nonmammalian metabolism, Limit of Detection, Naled toxicity, Reference Standards, Reproducibility of Results, Tissue Distribution, Toxicokinetics, Uncertainty, Acetylcholinesterase drug effects, Cholinesterase Inhibitors analysis, Cholinesterase Inhibitors pharmacokinetics, Lasers, Mass Spectrometry methods, Naled analysis, Naled pharmacokinetics, Zebrafish embryology
- Abstract
The zebrafish embryo is an important model in ecotoxicology but the spatial distribution of chemicals and the relation to observed effects is not well understood. Quantitative imaging can help to gain insights into the distribution of chemicals in the zebrafish embryo. Laser ablation inductively coupled plasma-mass spectrometry (LA-ICP-MS) is used to quantify the uptake and the uptake kinetics of the bromine (Br) containing organophosphate naled (Dibrom®, dimethyl-1,2-dibromo-2,2-dichloroethylphosphate) and its distribution in zebrafish embryos using Br as the marker element. During exposure, the Br amounts increase in the embryos parallel to the irreversible inhibition of the acetylcholinesterase (AChE). The final amount of Br in the embryo (545 pmol/embryo) corresponds to a 280-fold enrichment of naled from the exposure solution. However, LC-MS/MS analyses showed that the internal concentration of naled remained below the LOD (7.8 fmol/embryo); also the concentration of its known transformation product dichlorvos remained low (0.85 to 2.8 pmol/embryo). These findings indicate the high reactivity and high transformation rate of naled to other products than dichlorvos.
12 C normalized intensity distributions of Br in the zebrafish embryo showed an enrichment of Br in its head region. Kernel density estimates of the LA-ICP-MS data were calculated and outline the high reproducibility between replicated and the shift in the Br distribution during exposure. The Br enrichment indicates a preferential debromination or direct covalent reaction of naled with AChE in this region. Graphical abstract ᅟ.- Published
- 2019
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