Toxicokinetic Toxicodynamic (TKTD) Modeling of Ag Toxicity in Freshwater Organisms: Whole-Body Sodium Loss Predicts Acute Mortality Across Aquatic Species

Abstract

ToxicoKinetic ToxicoDynamic (TKTD) models are considered essential tools to further advance acute toxicity prediction of metals for a range of species and exposure conditions, but they are currently underutilized. We present a mechanistic TKTD model for acute toxicity prediction of silver (Ag) in freshwater organisms. In this new approach, we explicitly link relevant TKTD processes to species (physiological) characteristics, which facilitates model application to other untested freshwater organisms. The model quantifies the reduction in whole-body sodium concentration over time as a function of the target site inhibition over time, the target site density and the species-specific sodium turnover rate. Freshwater species are assumed to die instantly when they have lost a critical amount of their initial whole-body sodium concentration. Results show that mortality is significantly related to sodium loss (r(2) = 0.86) for various aquatic organisms and exposure durations. The model accurately predicts lethal effect concentrations for different freshwater organisms, including Daphnia magna, rainbow trout and juvenile crayfish, and is able to capture the observed size-specific variation of nearly 2 orders of magnitude in empirical LC50s.

Acute Cd Toxicity, Metal Accumulation, and Ion Loss in Southern Catfish (Silurus meridionalis Chen)

“…The consistency of the whole-body Na + content of dead fish across all exposure concentrations ( Figure 4 ) suggests that there is a critical Na + level, circa 34.54 μmol/g wet weight, below which survival is no longer possible. Our findings provide new evidence supporting the research of Veltman et al (2014), who concluded that when the Na ion concentration in the body of freshwater aquatic organisms is below a certain threshold, it leads to death [ 42 ]. Our results are also consistent with the conclusion that the significance of the exposure of zebrafish ( Danio rerio ) to Cd is related to a threshold of Na ion concentration [ 73 ].…”

“…Following Cd exposure, the main mechanism of fish toxicity is the disturbance of Na + and Ca 2+ ion homeostasis [ 14 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ]. Whole body Na + levels in zebrafish ( Danio rerio ) and rainbow trout ( Oncorhynchus mykiss ) are commonly used as indicators for acute and subacute Cd 2+ toxicity in fish [ 14 , 15 , 36 ].…”

Ecological relevance of biomarkers in monitoring studies of macro-invertebrates and fish in Mediterranean rivers

“…A two-step process of validation consists of using laboratory tests to determine cause-effect relationships between stressors and biomarkers followed by field studies to test for the strength of these relationships under a variable degree of complexity in natural systems. Only when a solid knowledge of biomarker responses is reached, and the understanding of the target system is sufficient, we can truly appraise the magnitude of health disorders in individuals and correctly assign risk for ecosystems using modelling approaches (Lombardo et al, 2015;Veltman et al, 2014).…”

Incorporating Suborganismal Processes into Dynamic Energy Budget Models for Ecological Risk Assessment

“…This remarkably simple model assumed that functional receptors are knocked out by the chemical, and functional receptors are turned into nonfunctional ones. Veltman et al (2014) extended this approach to predict Na loss and acute mortality in several aquatic species. Enzyme (acetylcholinesterase) inhibition was also considered in the time-dependent accrual of damage on the molecular level to explain differential sensitivity at the organism level in Daphnia magna (Kretschmann et al , 2012.…”