Particle size-dependent effects of silver nanoparticles on swim bladder damage in zebrafish larvae.

Particle size-dependent biological effects of silver nanoparticles (AgNPs) are of great interest; however, the mechanism of action of silver ions (Ag+) released from AgNPs concerning AgNP particle size remains unclear. Thus, we evaluated the influence of particle size (20, 40, 60, and 80 nm) on the acute 96-h bioaccumulation and toxicity (swim bladder damage) of AgNPs in zebrafish (Danio rerio) larvae, with a focus on the mechanism of action of Ag+ released from differently sized AgNPs. The 40- and 60-nm AgNPs were more toxic than the 20- and 80-nm versions in terms of inflammation and oxidative damage to the swim bladder, as indicated by inhibition of type 2 iodothyroxine deiodinase enzyme activity, mitochondrial injury, and reduced 30-50% adenosine triphosphate content. Furthermore, up-regulation and down-regulation of swim bladder development-related gene expression was not observed for pbx1a and anxa5, but up-regulation expression of shha and ihha was observed with no statistical significance. That 20-nm AgNPs were less toxic was attributed to their rapid elimination from larvae in comparison with the elimination of 40-, 60-, and 80-nm AgNPs; thus, less Ag+ was released in 20-nm AgNP-exposed larvae. Failed inflation of swim bladders was affected by released Ag+ rather than AgNPs themselves. Overall, we reveal the toxicity contribution of Ag+ underlying the observed size-dependent effects of AgNPs and provide a scientific basis for comprehensively assessing the ecological risk and biosafety of AgNPs.

Effect of dissolved organic matter on the bioavailability and toxicity of cadmium in zebrafish larvae: Determination based on toxicokinetic-toxicodynamic processes.

The presence of dissolved organic matter (DOM) strongly influences the bioavailability of metals in aquatic environments; however, the association between the binding activities and the concentrations of DOM compositions is not well documented, leading to uncertainties in metal toxicity assessment. We creatively quantify the mitigation and acceleration effects of DOM compositions on cadmium (Cd) bioaccumulation and toxicity in zebrafish larvae using abiotic ligand (ABLs) and biotic ligand (BLs) in a toxicokinetic-toxicodynamic (TK-TD) model. The BL-TK-TD model could accurately predict the protective effect of fulvic acid while overestimating the complexing capacity of citric acid. The model also could successfully simulate the protective effects of native DOM in most cases from 32 natural water bodies in China. The observed LC50 values of Cd showed a peak effect for the native DOM fraction comprising hydrophilic acidic contents (3.55 ± 0.44 mg L - 1) in natural water from 32 sites. The BL-TK-TD model provides practically useful information to identify the effect of different DOM compositions on metal bioavailability and toxicity in aquatic environments and guides future water management policies aimed at controlling aquatic heavy metal pollution.

Understanding the effects of metal pre-exposure on the sensitivity of zebrafish larvae to metal toxicity: A toxicokinetics-toxicodynamics approach.

Organisms are increasingly tolerant to metal toxicity in the natural ecosystems, which did not match the results of the environmental risk assessment (ERA) of metals based on toxicity data from organisms in the laboratory. Studies have described the effects of pre-exposure to metals on metal toxicity tolerance in terms of the toxicokinetic (TK) process; however, the toxicodynamic (TD) process may be more susceptible to metal pre-exposure. Therefore, to determine whether pre-exposure to low concentrations of silver (Ag) or cadmium (Cd) affects the metal TK and TD processes of zebrafish (Danio rerio) larvae, we investigated four TK-TD model parameters that control tolerance and sensitivity to metal toxicity on the survival. Our results showed that the killing rate (ks) of larvae exposed to high Cd concentrations was significantly lower following pre-exposure to 10 µg/L Cd than that of larvaenot pre-exposed. However, the ks for high Ag concentrations was significantly higher in zebrafish larvae following pre-exposure to 2 µg/L Ag than in larvae not pre-exposed. In other words, a one-day pre-exposure to 2 µg/L Ag rendered the larvae more sensitive to Ag during a subsequent 4-day exposure to higher Ag concentrations, whereas a one-day pre-exposure to 10 µg/L Cd rendered the larvae more tolerance to Cd during a subsequent 4-day exposure to higher Cd concentrations. Our results further the current understanding of toxic metal tolerance mechanisms, both in TK and TD processes, and they will guide future laboratory studies to assess actual pre-exposure scenarios that occur in natural environments. Thus, our study can help reduce uncertainty in testing and improve ecological management concerning metal risk assessments.

Predicting copper toxicity in zebrafish larvae under complex water chemistry conditions by using a toxicokinetic-toxicodynamic model.

Multiple water chemistry parameters influence metal toxicity in natural waters and accurate quantification of those influences may accelerate the development of site-specific water quality criteria (WQC) and further execute metal risk assessment for better protection of aquatic biota. Here, we investigated the effects of water chemistry parameters on copper (Cu) toxicity of larval zebrafish (Danio rerio) and then incorporated the effects of key parameters in a Toxicokinetic and Toxicodynamic (TK-TD) model. Further, the proposed TK-TD model was used to predict Cu toxicity in laboratory artificial waters as well as natural water samples. The predictive performance of the TK-TD model was evaluated in comparison to the biotic ligand model (BLM). The results showed that increasing Ca, Mg, pH, and fulvic acid (FA) levels significantly mitigated Cu toxicity in larvae, while K and Na levels had no significant effect on Cu toxicity. A predictive TK-TD model based on these data described 91 % of Cu accumulation and 87 % of survival of larvae exposed to Cu under 0, 2.5, 5, 10 mg/L FA. Compared with BLM, TK-TD model predicted better Cu accumulation and toxicity for an independent dataset in low DOC concentration (<10.95 mg L-1) of 9 sites in Haihe river (Tianjin, China) media during 96 h exposure. The BLM under-predicted the acute Cu toxicity to larvae when compared with observed values. In high DOC concentration (13.12-17.78 mg L-1) among three field sites, BLM and TK-TD model both under-predicted the acute Cu toxicity to larvae when compared with observed values. Our research provides a TK-TD approach for predicting Cu toxicity under complex water chemistry conditions and deriving Cu-WQC in different scenarios where there exist limits for using the BLM.