Development of a novel mathematical model using a group contribution method for prediction of ionic liquid toxicities

A new mathematical model has been developed that expresses the toxicities (EC₅₀ values) of a wide variety of ionic liquids (ILs) towards the freshwater flea Daphnia magna by means of a quantitative structure-activity relationship (QSAR). The data were analyzed using summed contributions from the cations, their alkyl substituents and anions. The model employed multiple linear regression analysis with polynomial model using the MATLAB software. The model predicted IL toxicities with R² = 0.974 and standard error of estimate of 0.028. This model affords a practical, cost-effective and convenient alternative to experimental ecotoxicological assessment of many ILs.     

QSAR development and bioavailability determination: The toxicity of chloroanilines to the soil dwelling springtail Folsomia candida

Quantitative structure–activity relationships (QSARs) are an established tool in environmental risk assessment and a valuable alternative to the exhaustive use of test animals under REACH. In this study a QSAR was developed for the toxicity of a series of six chloroanilines to the soil-dwelling collembolan Folsomia candida in standardized natural LUFA2.2 soil. Toxicity endpoints incorporated in the QSAR were the concentrations causing 10% (EC10) and 50% (EC50) reduction in reproduction of F. candida. Toxicity was based on concentrations in interstitial water estimated from nominal concentrations in the soil and published soil–water partition coefficients. Estimated effect concentrations were negatively correlated with the lipophilicity of the compounds. Interstitial water concentrations for both the EC10 and EC50 for four compounds were determined by using solid-phase microextraction (SPME). Measured and estimated concentrations were comparable only for tetra- and pentachloroaniline. With decreasing chlorination the disparity between modelled and actual concentrations increased. Optimisation of the QSAR therefore could not be accomplished, showing the necessity to move from total soil to (bio)available concentration measurements.     

多元逐步回归对苯胺类化合物结构与毒性模型研究

采用Chemoffice6．0中MOPAC-AMl量子化学法计算了24种苯胺类化合物的6种量子化学结构参数．其中取17个化合物作为样本集对-lgEC50进行多元逐步回归分析．得到最佳方程．经自由度校正的回归系数R=0．985。应用所建立的QSAR模型验证了苯胺类化合物的EC50值．并通过“Jackknife”中的逐一抽取法进行模型检验，得出该模型具有很好的稳定性．平均残差仅为0．05个对数单位．小于文献值。经过7个预测样本对该模型进行验证．结果表明．该模型具有很好的预测能力。同时分析了苯胺类化合物的毒性机理。     

The effect of nitroaromatics' composition on their toxicity in vivo: novel, efficient non-additive 1D QSAR analysis

Novel 1D QSAR approach that allows analysis of non-additive effects of molecular fragments on toxicity has been proposed. Twenty-eight nitroaromatic compounds including some well-known explosives have been chosen for this study. The 50% lethal dose concentration for rats (LD50) was used as the estimation of toxicity in vivo to develop 1D QSAR models on the framework of Simplex representation of molecular structure. The results of 1D QSAR analysis show that even the information about the composition of molecules provides the main trends of toxicity changes. The necessity of consideration of substituents' mutual impacts for the development of adequate QSAR models of nitroaromatics' toxicity was demonstrated. Statistic characteristics for all the developed partial least squares QSAR models, except the additive ones are quite satisfactory (R2=0.81-0.92; Q2=0.64-0.83; R2 test=0.84-0.87). A successful performance of such models is due to their non-additivity i.e. possibility of taking into account the mutual influence of substituents in benzene ring which plays the governing role for toxicity change and could be mediated through the different C-H fragments of the ring. The correspondence between observed and predicted by these models toxicity values is good. This allowing combine advantages of such approaches and develop adequate consensus model that can be used as a toxicity virtual screening tool.     

Multivariate toxicity profiles and QSAR modeling of non-dioxin-like PCBs--an investigation of in vitro screening data from ultra-pure congeners

The non-dioxin-like PCBs (NDL-PCBs) found in food and human samples have a complex spectrum of adverse effects, but lack a detailed risk assessment. The toxicity profiles of 21 carefully selected PCBs (19 NDL-PCBs) were identified by in vitro screening in 17 different assays on specific endpoints related to neurotoxicity, endocrine disruption and tumor promotion. To ensure that the test results were not affected by polychlorinated dioxins, dibenzofurans or DL-PCB contaminants, the NDL-PCB congeners were thoroughly purified before testing. Principal component analysis (PCA) was used to derive general toxicity profiles from the in vitro screening data. The toxicity profiles indicated different structure-activity relationships (SAR) and distinct mechanisms of action. The analysis also indicated that the NDL-PCBs could be divided into two groups. The first group included generally smaller, ortho-substituted congeners, comprising PCB 28, 47, 51, 52, 53, 95, 100, 101, 104 and 136, with PCB 95, 101 and 136 as generally being most active. The second group comprising PCB 19, 74, 118, 122, 128, 138, 153, 170, 180 and 190 had lower biological activity in many of the assays, except for three endocrine-related assays. The most abundant congeners, PCB 138, 153, 170, 180 and 190, cluster in the second group, and thereby show similar SAR. Two quantitative structure-activity relationship (QSAR) models could be developed that added information to the SAR and could aid in risk assessments of NDL-PCBs. The QSAR models predicted a number of congeners as active and among these e.g., PCB 18, 25, 45 and 49 have been found in food or human samples.     

The aquatic toxicity of anionic surfactants to Daphnia magna--a comparative QSAR study of linear alkylbenzene sulphonates and ester sulphonates

This paper develops quantitative structure activity relationships (QSARs) for the acute aquatic toxicity of the anionic surfactants linear alkylbenzene sulphonates (LAS) and ester sulphonates (ES) to Daphnia magna, the aim being to investigate the modes of action by comparing the QSARs for the two types of surfactant. The generated data for ES have been used to develop a QSAR correlating toxicity with calculated log P values: log(1/EC50)= 0.78 log P+1.37. This equation has an intercept 1.1 log units lower than a QSAR for linear alkylbenzene sulphonates (LAS). The findings suggest that either ES surfactants act by a different mode of action to LAS and other anionic surfactants or the log P calculation method introduces a systematic overestimate when applied to ES.     

A comparison of DEMETRA individual QSARs with an index for evaluation of uncertainty

Quantitative structure-activity relationships (QSARs) urgently need to be applied in regulatory programs. Many QSAR models can predict the effect of a wide range of substances to different endpoints, particularly in the case of ecotoxicity, but it is difficult to choose the most appropriate model on the basis of the requirements of the application. During the EC-funded project DEMETRA (www.demetra-tox.net) a huge number of QSAR models have been developed for the prediction of different ecotoxicological endpoints. DEMETRA individual models on rainbow trout LC50 after 96 h, water flea LC50 after 48 h and honey bee LD50 after 48 h have been used as a QSAR database to test the advantages of a new index for evaluating model uncertainty. This index takes into consideration the number of outliers (weighted on the total number of compounds) and their root mean square error. Application on the DEMETRA QSAR database indicated that the index can identify the models with the best performance with regard to outliers, and can be used, together with other classical statistical measures (e.g., the squared correlation coefficient), to support the evaluation of QSAR models.     

Peroxidase-mediated removal of endocrine disrupting compound mixtures from water

Several classes of oxidative enzymes have shown promise for efficient removal of endocrine disrupting compounds (EDCs) that are resistant to conventional wastewater treatments. Although the kinetics of reactions between individual EDCs and selected oxidative enzymes are well documented in the literature, there has been little investigation of reactions with EDC mixtures. This makes it impossible to predict how enzyme-mediated treatment systems will perform since wastewater effluents generally contain multiple EDCs. This paper reports pseudo-first order rate constants for a model oxidative enzyme, horseradish peroxidase (HRP), during single-substrate (k₁) and mixed-substrate (k_1-MIX) reactions. Measured values are compared with literature values of three Michaelis-Menten parameters: half-saturation constant (K_M), enzyme turnover number (k_CAT), and the ratio k_CAT/K_M. Published reports had suggested that each of these could be correlated with HRP reactivity towards EDCs in mixtures, and empirical results from this study show that K_M can be used to predict the sequence of EDC removal reactions within a particular mixture. We also observed that k_1-MIX values were generally greater than k₁ values and that compounds exhibiting greatest estrogenic toxicities reacted most rapidly in a given mixture. Finally, because K_M may be tedious to measure for every EDC of interest, we have constructed a quantitative structure-activity relationship (QSAR) model to predict these values. This model predicts K_M quite accurately (R² = 89%) based on two molecular characteristics: molecular volume and hydration energy. Its accuracy makes this QSAR a useful tool for predicting which EDCs will be removed most efficiently during enzyme treatment of EDC mixtures.     

Quantitative structure-activity relationship (QSAR) models for polycyclic aromatic hydrocarbons (PAHs) dissipation in rhizosphere based on molecular structure and effect size

Rhizoremediation is a significant form of bioremediation for polycyclic aromatic hydrocarbons (PAHs). This study examined the role of molecular structure in determining the rhizosphere effect on PAHs dissipation. Effect size in meta-analysis was employed as activity dataset for building quantitative structure-activity relationship (QSAR) models and accumulative effect sizes of 16 PAHs were used for validation of these models. Based on the genetic algorithm combined with partial least square regression, models for comprehensive dataset, Poaceae dataset, and Fabaceae dataset were built. The results showed that information indices, calculated as information content of molecules based on the calculation of equivalence classes from the molecular graph, were the most important molecular structural indices for QSAR models of rhizosphere effect on PAHs dissipation. The QSAR model, based on the molecular structure indices and effect size, has potential to be used in studying and predicting the rhizosphere effect of PAHs dissipation.     

Ecotoxicological responses of the earthworm Eisenia fetida exposed to soil contaminated with HHCB

Although polycyclic musks have been shown to cause lethal and sub-lethal effects on organisms, their biochemical toxicity to earthworms is not well understood. In the current study, we investigated the responses of antioxidant systems and lipid peroxidation after exposing Eisenia fetida to soil contaminated with 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethyl-cyclopenta-γ-2-benzopyran (HHCB). Significant increase in lipid peroxidation level was observed on day 14 at two high concentrations, 50 and 100 mg kg⁻¹. Among antioxidant enzymes, the primary response to chronic HHCB exposure can be attributed to superoxide dismutase (SOD) and catalase (CAT). Of the two enzymes, SOD exhibited more sensitive response to HHCB stress. In addition, these two enzymes could have a combined effect on fighting damage by reactive oxygen species, evidenced by a marked relationship between lipid peroxidation and enzyme activity. On the other hand, dose-dependent inhibition of peroxidase (POD) activity has been observed throughout the test. The results suggest that the variations in investigated parameters of E. fetida could be used as responsive biomarkers for oxidative stress caused by HHCB in a soil environment.     

A Protocol to Select High Quality Datasets of Ecotoxicity Values for Pesticides

Abstract

The key to any QSAR model is the underlying dataset. In order to construct a reliable dataset to develop a QSAR model for pesticide toxicity, we have derived a protocol to critically evaluate the quality of the underlying data. In developing an appropriate protocol that would enable data to be selected in constructing a QSAR, we concentrated on one toxicity end point, the 96 h LC50 from the acute rainbow trout study. This end point is key in pesticide regulation carried out under 91/414/EEC. The dataset used for this exercise was from the US EPA-OPP database.     

Application of biomarkers to assess the condition of European Marine Sites

A series of European Marine Sites has been designated as Special Areas of Conservation (SAC) in England. The aim of this study was to develop a practical methodology to assess the condition of SACs by applying a suite of biomarkers. Biomarkers were applied to the blue mussel Mytilus edulis and the shore crab Carcinus maenas from the Fal and Helford SAC (Cornwall). Individual biomarkers provided useful diagnostic information on the activity of certain classes of contaminants and an integrated Biomarker Response Index (BRI) was used to achieve a more holistic understanding of the condition of the SAC. The BRI indicated that the general health of both organisms was impacted in the upper part of the SAC (Fal Estuary) which correlated well with known chemical hotspots and sources of contamination. The BRI allows a pragmatic way to prioritise SAC sites that may require further investigative studies.     

Converging hazard assessment of gold nanoparticles to aquatic organisms

The gold nanoparticles (Au-NPs) are being increasingly used because of their huge diversity of applications, and consequently, elevated levels in the environment are expected. However, due to their physico-chemical properties and functionalization a high variety of Au-NPs can be found, and complete toxicological information for each type of Au-NPs still lacks, and even, the toxicological information for the same species is sometimes contradictory. Therefore, hazard assessment should be done case by case. Hence, the objective of this study was to obtain ecotoxicological information of the same Au-NPs in aquatic organisms and to find a rationale for Au-NPs toxicity. For such a purpose, bare and hyaluronic acid capped Au-NPs (12.5 nm) along with Au-NPs bulk material were tested on freshwater algae, Daphnia and zebrafish. Results showed that while gold nanoparticles were found to be harmless to the tested organisms, the soluble gold showed to be toxic to algae and Daphnia, with an LC₅₀ between 1 and 2 mg L⁻¹. Comparing our results with those gathered in the literature, it appears that a common hazard assessment of Au-NPs on the studied organisms can be elucidated.     

Use of reporter-gene based bacteria to quantify phenanthrene biodegradation and toxicity in soil

A phenanthrene-degrading bacterium, Sphingomonas paucimobilis EPA505 was used to construct two fluorescence-based reporter strains. Strain D harboring gfp gene was constructed to generate green fluorescence when the strain started to biodegrade phenanthrene. Strain S possessing gef gene was designed to die once phenanthrene biodegradation was initiated and thus to lose green fluorescence when visualized by a live/dead cell staining. Confocal laser scanning microscopic observation followed by image analysis demonstrates that the fluorescence intensity generated by strain D increased and the intensity by strain S decreased linearly at the phenanthrene concentration of up to 200 mg/L. Such quantitative increase and decrease of fluorescence intensity in strain D (i.e., from 1 to 11.90 ± 0.72) and strain S (from 1 to 0.40 ± 0.07) were also evident in the presence of Ottawa sand spiked with the phenanthrene up to 1000 mg/kg. The potential use of the reporter strains in quantitatively determining biodegradable or toxic phenanthrene was discussed.     

Bioadsorption and bioaccumulation of chromium trivalent in Cr(III)-tolerant microalgae: A mechanisms for chromium resistance

Anthropogenic activity constantly releases heavy metals into the environment. The heavy metal chromium has a wide industrial use and exists in two stable oxidation states: trivalent and hexavalent. While hexavalent chromium uptake in plant cells has been reported that an active process by carrying essential anions, the cation Cr(III) appears to be taken up inactively. Dictyosphaerium chlorelloides (Dc1M), an unicellular green alga is a well-studied cell biological model organism. The present study was carried out to investigate the toxic effect of chromium exposures on wild-type Cr(III)-sensitive (Dc1M^wt) and Cr(III)-tolerant (Dc1M^Cr(III)R30) strains of these green algae, and to determine the potential mechanism of chromium resistance. Using cell growth as endpoint to determine Cr(III)-sensitivity, the IC₅₀₍₇₂₎ values obtained show significant differences of sensitivity between wild type and Cr(III)-tolerant cells. Scanning electron microscopy (SEM) showed significant morphological differences between both strains, such as decrease in cell size or reducing the coefficient of form; and transmission electron microscopy (TEM) revealed ultrastructural changes such as increased vacuolization and cell wall thickening in the Cr(III)-tolerant strain with respect to the wild-type strain. Energy dispersive X-ray analysis (SEM/XEDS) revealed that Cr(III)-tolerant D. chlorelloides cells are able to accumulate considerable amounts of chromium distributed in cell wall (bioadsorption) as well as in cytoplasm, vacuoles, and chloroplast (bio-accumulation). Morphological changes of Cr(III)-tolerant D. chlorelloides cells and the presence of these electron-dense bodies in their cell structures can be understood as a Cr(III) detoxification mechanism.     

Impact of dissolved organic matter on bioavailability of chlorotoluron to wheat

Chlorotoluron (Chl) is a phenylurea herbicide and is widely used for controlling weeds. While it has brought great benefits to crop production, it has also resulted in contamination to ecosystem. In this study, we investigated accumulation of chlorotoluron (Chl) and biological responses of wheat plants as affected by dissolved organic matter (DOM). Wheat seedlings grown under 10 mg kg⁻¹ Chl for 4 d showed a low level of chlorophyll accumulation and damage to plasma membrane. The growth was inhibited by exposure of chlorotoluron. Treatment with 50 mg DOC kg⁻¹ DOM derived either from sludge (DOM-SL) or straw (DOM-ST) attenuated the chlorotoluron toxicity to plants. Both DOMs decreased activities of catalase, peroxidase and superoxide dismutase in Chl-treated seedlings. However, an increased glutathione S-transferases activity was observed under the same condition. Wheat plants treated with Chl in the presence of DOM accumulated less Chl than those treated with Chl alone. Moreover, in the presence of DOM, bioconcentration factor (BCF) decreased whereas translocation factors increased. Analyses with FT-IR spectra confirmed the regulatory role of DOMs in reducing Chl accumulation in wheat.