Model-based rationalization of mixture toxicity and accumulation in Triticum aestivum upon concurrent exposure to yttrium, lanthanum, and cerium

Rare earth elements (REEs) often co-exist in the environment, but predicting their 'cocktail effects' is still challenging, especially for high-order mixtures with more than two components. Here, we systematically investigated the toxicity and accumulation of yttrium, lanthanum, and cerium mixtures in Triticum aestivum following a standardized bioassay. Toxic effects of mixtures were predicted using the reference model of Concentration Addition (CA), Ternary model, and Ternary-Plus model. Interactions between the REEs in binary and ternary mixtures were determined based on external and internal concentrations, and their magnitude estimated from the parameters deviated from CA. Strong antagonistic interactions were found in the ternary mixtures even though there were no significant interactions in the binary mixtures. Predictive ability increased when using the CA model, Ternary model, and Ternary-Plus model, with R-2 = 0.78, 0.80, and 0.87 based on external exposure concentrations, and R-2 = 0.72, 0.73, and 0.79, respectively based on internal concentrations. The bioavailability-based model WHAM-F-TOX explained more than 88 % and 85 % of the toxicity of binary and ternary REE treatments, respectively. Our result showed that the Ternary-Plus model and WHAM-F-TOX model are promising tools to account for the interaction of REEs in mixtures and could be used for their risk assessment.