Predicting cadmium and lead toxicities in zebrafish (Danio rerio) larvae by using a toxicokinetic–toxicodynamic model that considers the effects of cations

Feng, Jianfeng; Gao, Yongfei; Chen, Min; Xu, Xin; Huang, Mengdi; Yang, Tong; Chen, Na; Zhu, Lin

doi:10.1016/j.scitotenv.2018.01.068

Cited by 15 publications

(14 citation statements)

References 47 publications

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“…Support for our approach comes from the measurements by Feng et al (2018) of Cd accumulation in Danio rerio, which showed that 50% of the maximum accumulation occurred within 24 hours, similar to our results ( Figure 1).…”

Section: Can Temporal Variability In αM Be Parameterised and Quantified?supporting

confidence: 88%

Systematic analysis of freshwater metal toxicity with WHAM-FTOX

2019

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Section: Can Temporal Variability In αM Be Parameterised and Quantified?supporting

confidence: 88%

Systematic analysis of freshwater metal toxicity with WHAM-FTOX

2019

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“…In addition, knowing chemical concentrations in organs is fundamental to understand dose-response relationships [13,14]. Internal concentrations are often difficult to measure, but physiologically-based pharmacokinetic (PBPK) models can estimate them [15,16]. PBPK models connect anatomy, physiology, and biochemical processes to understand and compute a chemical's fate in the body.…”

Section: Introductionmentioning

confidence: 99%

Development of a generic zebrafish embryo PBPK model and application to the developmental toxicity assessment of valproic acid analogs

Siméon

Brotzmann

Fisher

et al. 2020

Reproductive Toxicology

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In order to better explain, predict, or extrapolate to humans the developmental toxicity effects of chemicals to zebrafish (Danio rerio) embryos, we developed a physiologically-based pharmacokinetic (PBPK) model designed to predict organ concentrations of neutral or ionizable chemicals, up to 120 hours post-fertilization. Chemicals' distribution is modeled in the cells, lysosomes, and mitochondria of ten organs of the embryo. The model's partition coefficients are calculated with sub-models using physicochemical properties of the chemicals of interest. The model accounts for organ growth and changes in metabolic clearance with time. We compared ab initio model predictions to data obtained on culture medium and embryo concentrations of valproic acid (VPA) and nine analogs during continuous dosing under the OECD test guideline 236. We further improved the predictions by estimating metabolic clearance and partition coefficients from the data by Bayesian calibration. We also assessed the performance of the model at reproducing data published by Brox et al. (2016) on VPA and 16 other chemicals. We finally compared dose-response relationships calculated for mortality and malformations on the basis of predicted whole embryo concentrations versus those based on nominal water concentrations. The use of target organ concentrations substantially shifted the magnitude of doseresponse parameters and the relative toxicity ranking of chemicals studied.

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“…It is worth noting that the effects of cations in the exposure medium on the toxicity of different metals are different, 72 but these effects were not considered in the present study. We used ultrapure water as the exposure solution to remove the influence of cations on different metals.…”

Section: Lethal and Sublethal Toxicitymentioning

confidence: 99%

Role of Toxicokinetic and Toxicodynamic Parameters in Explaining the Sensitivity of Zebrafish Larvae to Four Metals

Yang

Feng

Gao

et al. 2021

Environ. Sci. Technol.

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Given the persistence and toxic potencies of metal contaminants in ecosystems, animals, and human beings, they are considered to be hazardous global pollutants. While the lethality of metal toxicities (e.g., LC50) can significantly vary, even within the same species, the underlying mechanisms are less well-understood. In this study, we developed a subcellular two-compartment toxicokinetic-toxicodynamic (TK-TD) model for zebrafish larvae when exposed to four metals (cadmium, lead, copper, and zinc) to reveal whether differences in metal toxicity (LC50 values) were dominated by the TK or TD processes. Results showed that the subcellular TK and TD parameters of the four metals were significantly different, and the bioconcentration factor (BCF) value of copper was higher than those of the other metals. We also found that the TD parameter internal threshold concentration (C IT) was significantly positively correlated to the LC50 values (R 2 = 0.7), suggesting a dominant role of TD processes in metal toxicity. Furthermore, the combined parameter C IT /BCF for a metal-sensitive fraction (BCFMSF), which linked exposure to effects through the TK-TD approach, explained up to 89% of the variation in toxicity to the four metals. The present study suggests that the observed variation in toxicity of these four metals was mainly determined by TD processes but that TK processes should not be ignored, especially for copper.

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Predicting cadmium and lead toxicities in zebrafish (Danio rerio) larvae by using a toxicokinetic–toxicodynamic model that considers the effects of cations

Cited by 15 publications

References 47 publications

Systematic analysis of freshwater metal toxicity with WHAM-FTOX

Systematic analysis of freshwater metal toxicity with WHAM-FTOX

Development of a generic zebrafish embryo PBPK model and application to the developmental toxicity assessment of valproic acid analogs

Role of Toxicokinetic and Toxicodynamic Parameters in Explaining the Sensitivity of Zebrafish Larvae to Four Metals

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