Comparison of in silico models for prediction of Daphnia magna acute toxicity

Eight in silico modelling packages were evaluated and compared for the prediction of Daphnia magna acute toxicity from the viewpoint of the European legislation on chemicals, REACH. We tested the following models: Discovery Studio (DS) TOPKAT, ACD/Tox Suite, ADMET Predictor?, ECOSAR (Ecological Structure Activity Relationships), TerraQSAR?, T.E.S.T. (Toxicity Estimation Software Tool) and two models implemented in VEGA on 480 industrial compounds for 48-h median lethal concentrations (LC₅₀) to D. magna, matching them with experimental values. The quality of the estimates was compared using a standard statistical review and an additional classification approach in which the hazard predictions were grouped using well-defined regulatory criteria. The regression parameters, correlation coefficient being the most influential, showed that four models (ADMET Predictor?, DS TOPKAT, TerraQSAR? and VEGA DEMETRA) had similar reliability. These performed better than the others, but the coefficient of determination was still low (r² around 0.6), considering that at least half the predicted compounds were inside the training sets. Additionally, we grouped the results in four defined toxicity classes. TerraQSAR? gave 60% of correct classifications, followed by DS TOPKAT, ADMET Predictor? and VEGA DEMETRA, with 56%, 54% and 48%, respectively. These results highlight the challenges associated with developing reliable and easily applied acceptability criteria for the regulatory use of QSAR models to D. magna acute toxicity.     

Comparative evaluation of the effects of pesticides in acute toxicity luminescence bioassays

Acute toxicity of pesticides in water was assessed singly and in mixtures using the responses of the luminescent bacterium Vibrio fischeri (BioTox™), the aquatic invertebrate Daphnia magna (Daphtoxkit™), and the MitoScan™ assay. The latter utilized fragmented mitochondria to enzymatically convert β-nicotinamide adenine dinucleotide (NADH) to its oxidized form, NAD⁺. The rate of the conversion being sensitive to type and concentration of toxicants. The pesticides tested were Carbofuran (2,3-dihydro-2,2-dimethylbenzofuran-7-yl methylcarbamate), Cyromazine (N-cyclopropyl-1,3,5-triazine-2,4,6-triamine), Fenamiphos (ethyl 4-methylthio-m-tolyl isopropylphosphoramidate), and Formetanate (3-dimethylaminomethyleneiminophenyl methylcarbamate). The toxicity bioassays were characterized in terms of relative sensitivity, reproducibility, range of the linear response, and the ability to reveal synergistic/antagonistic interactions among toxicants. The D. magna assay was the most sensitive and best able to detect toxic interactions of mixtures. Also, unlike the other assays used, the response of the daphnid system was linear over a 10-fold change in pesticide concentration. Relative to the BioTox™, the MitoScan™ was 2- to 11-fold more sensitive for the compounds and mixtures tested. The EC₅₀ reproducibility of all tests was within ±20% coefficient of variation; however, the lowest observable effect concentration (LOEC) were only reproducible to ±35% on average. Cyromazine was the least toxic of the pesticides tested. To test the predictive value of the concept of concentration addition, toxicities of binary and quaternary mixtures of four different pesticides were analyzed. Synergistic/antagonistic responses were most frequently observed in testing with D. magna. Synergistic/antagonistic effects were seen only in 25 and 50% of the cases with the BioTox™ and the MitoScan™ assays, respectively.     

Acute toxicities of six manufactured nanomaterial suspensions to Daphnia magna

The rapid growth of nanotechnology is stimulating research on the potential environmental impacts of manufactured nanomaterials (MNMs). This paper summarizes a comprehensive study on the 48-h acute toxicity of water suspensions of six MNMs (i.e., ZnO, TiO₂, Al₂O₃, C₆₀, SWCNTs, and MWCNTs) to Daphnia magna, using immobilization and mortality as toxicological endpoints. The results show that the acute toxicities of all MNMs tested are dose dependent. The EC₅₀ values for immobilization ranged from 0.622 mg/L (ZnO NPs) to 114.357 mg/L (Al₂O₃ NPs), while the LC₅₀ values for mortality ranged from 1.511 mg/L (ZnO NPs) to 162.392 mg/L (Al₂O₃ NPs). In these tests, TiO₂, Al₂O₃, and carbon-based nanomaterials were more toxic than their bulk counterparts. Moreover, D. magna were found to ingest nanomaterials from the test solutions through feeding behaviors, which indicates that the potential ecotoxicities and environmental health effects of these MNMs cannot be neglected.     

Development of classification models for predicting chronic toxicity of chemicals to Daphnia magna and Pseudokirchneriella subcapitata

Both the acute toxicity and chronic toxicity data on aquatic organisms are indispensable parameters in the ecological risk assessment priority chemical screening process (e.g. persistent, bioaccumulative and toxic chemicals). However, most of the present modelling actions are focused on developing predictive models for the acute toxicity of chemicals to aquatic organisms. As regards chronic aquatic toxicity, considerable work is needed. The major objective of the present study was to construct in silico models for predicting chronic toxicity data for Daphnia magna and Pseudokirchneriella subcapitata. In the modelling, a set of chronic toxicity data was collected for D. magna (21 days no observed effect concentration (NOEC)) and P. subcapitata (72 h NOEC), respectively. Then, binary classification models were developed for D. magna and P. subcapitata by employing the k-nearest neighbour method (k-NN). The model assessment results indicated that the obtained optimum models had high accuracy, sensitivity and specificity. The model application domain was characterized by the Euclidean distance-based method. In the future, the data gap for other chemicals within the application domain on their chronic toxicity for D. magna and P. subcapitata could be filled using the models developed here.     

Correlation of molecular total surface area with organotin toxicity for biological and physicochemical applications

There exists a high correlation between molecular total surface area (TSA) values and diorganotin toxicity towards several distinct types of organisms. This correlation was found for N₂a neuroblastoma cells, 3T3 fibroblasts, Daphnia magna Rhithropanopeus harrisii and Ankistrodesmus falcatus. In the case of Rhithropanopeus harrisii, a high correlation was also found between TSA and toxicity for triorganotins as well. This study suggests that the relationship between TSA and toxicity is a function of the hydrophobicity of the organotin compounds rather than electronic or steric effects.     

Methiocarb Degradation by Electro-Fenton: Ecotoxicological Evaluation

This paper studies the degradation of methiocarb, a highly hazardous pesticide found in waters and wastewaters, through an electro-Fenton process, using a boron-doped diamond anode and a carbon felt cathode; and evaluates its potential to reduce toxicity towards the model organism Daphnia magna. The influence of applied current density and type and concentration of added iron source, Fe₂(SO₄)₃·5H₂O or FeCl₃·6H₂O, is assessed in the degradation experiments of methiocarb aqueous solutions. The experimental results show that electro-Fenton can be successfully used to degrade methiocarb and to reduce its high toxicity towards D. magna. Total methiocarb removal is achieved at the applied electric charge of 90 C, and a 450× reduction in the acute toxicity towards D. magna, on average, from approximately 900 toxic units to 2 toxic units, is observed at the end of the experiments. No significant differences are found between the two iron sources studied. At the lowest applied anodic current density, 12.5 A m⁻², an increase in iron concentration led to lower methiocarb removal rates, but the opposite is found at the highest applied current densities. The highest organic carbon removal is obtained at the lowest applied current density and added iron concentration.