The internal concentration of organic substances in fish embryos—A toxicokinetic approach

Abstract

In ecotoxicity assessment, the ambient exposure concentration is typically applied to quantify the toxic potential of xenobiotic substances. However, exposure and organism-related differences in bioconcentration often cause a considerable variability of toxicity data. This can be minimized by using the internal organism concentration, because toxicokinetic modifying factors are considered implicitly. In the present study, the relationship between ambient and internal concentration-time profiles was investigated for zebrafish (Danio rerio) embryos. The aim was to gain a better understanding and interpretation of exposure-based methods using this model organism. For this purpose, a simple and effective approach to determine the internal concentration was developed. Embryos were exposed to a series of 4 neutral organic substances (naphthalene, fluorene, fluoranthene, benz[a]anthracene) of different hydrophobicity for 72 h. The internal and ambient concentrations were measured at 8 to 9 time points. Kinetics of uptake and elimination were modeled using a first-order 1-compartment model. Biotransformation processes appeared to influence the internal concentrations of fluoranthene and benz[a]anthracene after 48 h. The bioconcentration factors (BCFs) obtained are in excellent agreement with those determined in previous studies using radiolabeled substances. The method demonstrated in the present study is a further step toward a refined ecotoxicity assessment using fish embryos, which links toxicity to the chemical concentration within the organism. This system may also be considered as an alternative to animal testing for BCF determination.

Differential sensitivity in embryonic stages of the zebrafish (Danio rerio): The role of toxicokinetics for stage-specific susceptibility for azinphos-methyl lethal effects

“…A differential uptake and distribution and the final corresponding bioavailable internal concentration could be caused by several factors such as changes in the properties of cellular membranes, expression of efflux transporter proteins (Luckenbach et al, 2014) or metabolic transformation (Kuhnert et al, 2013). However, analysis of the time course of internal concentration differences in uptake or elimination did not explain the different sensitivity: similar maximum concentrations were reached for all exposure windows with t 95 ranging from 1.6 to 4.7 h ( Table 4).…”

“…The time course of internal concentration was described by fitting a differential equation for a one-compartment model to the measured concentrations as described by (Kuhnert et al, 2013) but using the analytical solution [3] of the differential equation [2]. Since analysis of exposure concentrations indicate stable concentrations it was assumed that an equilibrium internal concentration would be reached:…”

“…Particularly, the embryos of the zebrafish (Danio rerio) represent a highly attractive and versatile model, given their ease of production, size, transparency, rapid development, as well as well characterized developmental genetics and suitability for high throughput analysis. Potential applications in toxicology range from the prediction of acute fish (Belanger et al, 2013a;Knöbel et al, 2012a;Lammer et al, 2009) and fish early life stage toxicity (Volz et al, 2011), determination of bioconcentration (Kuhnert et al, 2013), analyses of endocrine disruption (Brion et al, 2012;Thienpont et al, 2011), identification of organ toxicity (Scholz, 2013), and teratogenic effects (Brannen et al, 2010;Gustafson et al, 2012;Selderslaghs et al, 2012) to prediction of mammalian acute systemic toxicity (Ali et al, 2011). Most advanced is the prediction of acute fish toxicity ((Lammer et al, 2009); (Belanger et al, 2013b); (Knöbel et al, 2012b)) indicated also by the recently approved OECD guideline TG 236 for the Fish Embryo Acute Toxicity Test (Busquet et al, 2014).…”

Influence of the perivitelline space on the quantification of internal concentrations of chemicals in eggs of zebrafish embryos (Danio rerio)

“…Additionally commonly used solvents may change the permeability of the chorion (Kais et al, 2013). Until now only a limited number of studies investigate the uptake of chemicals in early life-stages of the ZFE in combination with (Brox et al, 2014;Stanley et al, 2009) or without (Kühnert et al, 2013;Petersen and Kristensen, 1998) dechorionation. The dechorionation of early life-stages of the ZFE is proposed for exposure experiments starting at 24 hpf (Henn and Braunbeck, 2011).…”

Bioconcentration and Metabolism of Emodin in Zebrafish Eleutheroembryos

“…The degree of the bioconcentration can be expressed as the bioconcentration factor (BCF), which is defined as the ratio between the concentration of the chemical in the organism and environment at steady state. Polycyclic aromatic hydrocarbons (PAHs), like naphthalene and anthracene, are a kind of hard-degraded substances with high BCF (Kuhnert et al, 2013). Since anthraquinones are derivatives of anthracene, they may have some properties similar to PAHs.…”