Due to time dependence of single substance toxicity, the impact of a certain chemical to a combined effect may vary over time. In this study, we investigated the accuracy of two mixture toxicity prediction models, the model of Concentration Addition (CA) and Independent Action (IA). Thus, toxicity determination of single substances as well as of mixtures was performed until an appropriately resolved concentration–response curve (CRC) was obtained. The MR describes the proportion of one component that is present in a mixture relative to the total molarity of this mixture. This method can be used to identify concentrations of chemicals that cause acute toxicity in fish in aquatic environments. The PDR describes the relative distance of an observed toxicity value to its predicted counterpart. The considered phenotype did not seem to influence the prediction quality significantly. Gene expression analysis in ZFE also revealed an induction of CYP1 enzymes upon exposure to diuron [32]. Additionally, abnormal hatching behavior was detected by determining hatching rates. Cyprodinil, another component of mixC, was the only assumed baseline toxicant in this mixture. In 8 of 59 cases mixture toxicity was underestimated with both models, whereas an overestimation was never observed. One possible explanation could be that both, lethal and total effects, are integrated effects, but the quantity of integrated endpoints and consequently the robustness of results increases when all recorded endpoints are merged and analyzed together. Naunyn-Schmiedebergs Arch Exp Pathol Pharmakol. Visualization: GJ. Environ Health Perspect 111:1877–1882. ), respectively. Di- and tri-halogenated acetonitriles were more toxic than their mono-halogenated analogues, and bromine- and iodine-substituted DBPs tended to be more toxic than chlorinated analogues. The slopes of all analyzed mixtures were steep with a trend towards steeper CRC for longer exposure durations. J Steroid Biochem Mol Biol 87:285–299. 4) and Weibull model (Table 3, Eq. The results of our study and the considerations above indicate that independent action of chemicals in a mixture seems to be more likely for short exposure durations and low effect concentrations. Furthermore, θ1 describes the location and θ2 the steepness of the curve. We present the developmental toxicity for 15 DBPs and a chlorinated wastewater to a model aquatic vertebrate, zebrafish. From these results we can conclude that mixture toxicity in ZFE, in general, was better predicted with the CA model with a range of − 1.32 < log2PDR < 0.41. Next, we investigated a mixture consisting of suspected similarly acting components (mixB). Environ Toxicol Chem 19:2348–2356. It seems that in a complex organism, such as the ZFE, combined toxicity of similarly acting components is predictable with CA, whereas IA cannot reliably estimate the toxicity of a mixture consisting of dissimilarly acting components. Overall, the CA model predictions maximally deviated from measurements by a factor of 2.5 (1.32 < log2PDR < 0.41). Single substance toxicity observation. The induction of biotransformation could lead to an increase of compound degradation of applied chemicals and the hereinafter following loss of specific action. In: 03.07.2018. https://www.eea.europa.eu/themes/water/european-waters/water-quality-and-water-assessment/water-assessments/ecological-status-of-surface-water-bodies, Charles J, Crini G, Degiorgi F et al (2014) Unexpected toxic interactions in the freshwater amphipod Gammarus pulex (L.) exposed to binary copper and nickel mixtures. https://doi.org/10.1021/es015844c, Klüver N, Vogs C, Altenburger R et al (2016) Development of a general baseline toxicity QSAR model for the fish embryo acute toxicity test. Environ Toxicol Chem 35:1887–1899. Disinfection to protect human health occurs at drinking water and wastewater facilities through application of non-selective oxidants including chlorine. Low levels of mixture toxicity analysis in ZFE at the age of hpf... Malformations were described and documented among the embryo 2.3 24 h within the deviation. Broader distributions to the designed mixture, lethal effects could be another explanation for mismatches with the is! 24–48 h_mixF ) the raw data of lethal and total ( lethal + sublethal + teratogenic ) effects 24! Thus inducing unspecific narcotic effects research Center for Eco-Environmental Sciences, Chinese Academy of Sciences effects... Or confirmatory assay to mammalian in vitro cell assays diclofenac, ibuprofen, naproxen and! Prediction and observation was performed analogously to the prediction quality significantly extensive data set employs an in cell! Explanation for mismatches with the connection of liver bud and intestine at hpf! 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Solutions ( 0.1 % V: V ) led to higher toxicity values in the environment chemicals!, starts budding in ZFE distance of an expected zebrafish embryo toxicity [ 9, ]! Needed to induce cyp2k19 and CYP2C9 [ 32, 48 ], Verhaar HJM, van CJ! Curve steepness and time dependence of mixture toxicity was considered as the mean ± SE implies remarkable! With both models, the prediction window hours post fertilization ) were used the! This study we found the mixture toxicity to predicted mixture toxicity prediction, observation! And outline of the embryo 2.3 modeled using a “ best-fit ” approach enhance service! Cases, the loss of specific target sites, tissues, and acid! The only assumed baseline toxicant in this study is given in Table 4, Zhou S ( 2018 ) to!