title: Toxicokinetics of Polar Chemicals in Zebrafish Embryo (Danio rerio): Influence of Physicochemical Properties and of Biological Processes.
abstract: The time-resolved uptake of 17 nonionic and ionic polar compounds (logD ≤ 2) with a diversity of functional groups into zebrafish embryos (ZFE) was studied over 96 h of exposure. Among them were pharmaceuticals, pesticides and plant active ingredients. Uptake rates for the diffusion controlled passive uptake through the ZFE membrane ranged from 0.02 to 24 h(-1) for the nonionic compounds and were slower for ionic compounds (<0.008-0.08 h(-1)). The study compounds did not enrich much in the ZFE (median bioconcentration factor of 1, max. 7). Biotransformation significantly influenced the internal concentration of some of the test compounds over time (benzocaine, phenacetin, metribuzin, phenytoin, thiacloprid, valproic acid). For benzocaine, valproic acid and phenacetin several transformation products (TPs) were observed by LC-MS already at early life-stages (before 28 hpf); for benzocaine the TPs comprised >90% of the initial amount taken up into the ZFE. For six compounds internal concentrations remained very low (rel. int. conc. < 0.2). Besides biotransformation (sulfamethoxazole), poor membrane permeability (cimetidine, colchicine) and also affinity to efflux transporters (atropine and chloramphenicol) are the likely reasons for these low internal concentrations. This study outlines that the uptake of polar compounds into ZFE is influenced by their physicochemical properties. However, biological processes, biotransformation and, likely, efflux can strongly affect the internal concentrations already in early developmental stages of the ZFE. This should be considered in future toxicokinetic modeling. The evaluation of the toxicity of chemicals by ZFE requires toxicokinetic studies of the test compounds and their TPs to increase comparability to effects in fish.
authors: Department of Analytical Chemistry, Helmholtz Centre for Environmental Research - UFZ , Permoserstrasse 15, 04318 Leipzig, Germany.
authors: Stephan
authors: S
authors: Brox
authors: Department of Analytical Chemistry, Helmholtz Centre for Environmental Research - UFZ , Permoserstrasse 15, 04318 Leipzig, Germany.
authors: Bettina
authors: B
authors: Seiwert
authors: Department Bioanalytical Ecotoxicology, Helmholtz Centre for Environmental Research - UFZ , Permoserstrasse 15, 04318 Leipzig, Germany.
authors: Eberhard
authors: E
authors: Küster
authors: Department of Analytical Chemistry, Helmholtz Centre for Environmental Research - UFZ , Permoserstrasse 15, 04318 Leipzig, Germany.
authors: Thorsten
authors: T
authors: Reemtsma
mesh_terms: D000818:Animals; D004625:Embryo, Nonmammalian / Q000187:drug effects*; D010575:Pesticides / Q000633:toxicity*; D004364:Pharmaceutical Preparations; D028321:Plant Preparations / Q000633:toxicity*; D066007:Toxicokinetics; D015027:Zebrafish / Q000196:embryology
chemical_list: D010575:Pesticides; D004364:Pharmaceutical Preparations; D028321:Plant Preparations