Yuanhui Zhao

QSAR study of the toxicity of benzoic acids to Vibrio fischeri, Daphnia magna and carp.

The toxicities of benzoic acids to Vibrio fischeri, Daphnia magna and carp were measured. The results showed that the toxicity to V. fischeri and Daphnia decreased in the order of bromo > chloro > fluoro approximately equal to aminobenzoic acids. The toxicity of substituted benzoic acids to carp and Daphnia was much lower that to V. fischeri. The results also showed that the toxicity of benzoic acids to Daphnia decreased as the pH increased. It is suggested that ionized and non-ionized forms have different toxic responses. The non-ionized form may play an important role in toxicity because the toxicity of benzoic acids to Daphnia greatly decreases as the pH increases. The toxicity of benzoic acids to Daphnia may operate through non-polar narcosis, based on the regression results between the toxicities and partition coefficients (log P) and apparent partition coefficients (log D). However, toxicity cannot be predicted from non-polar baseline models because the ionized and non-ionized form of benzoic acids have different contributions to toxicity. Compared with the single descriptors, the prediction of toxicity of the benzoic acids was improved remarkably by using log P with pKa and log P with ELUMO. For the toxicity of benzoic acids to V. fischeri, it is suggested that the toxic mechanism may be different from the mechanism in Daphnia and carp. A probable reason is that V. fischeri is a unicellular organism with low lipid content, and hence both ionized and non-ionized forms of benzoic acids can easily cross the cell membrane and contribute to toxicity.

QSAR study on the toxicity of substituted benzenes to the algae (Scenedesmus obliquus)

50% effective inhibition concentration 48h-EC50 of 40 substituted benzenes to the algae (Scenedesmus obliquus) was determined. The energy of the lowest unoccupied molecular orbital (E(LUMO)) was calculated by the quantum chemical method MOPAC6.0-AM1. By using E(LUMO) and the hydrophobicity parameter log K(OW) the quantitative structure-activity relationship model (QSAR) was developed: log1/EC50=0.272 logK(OW) - 0.659E(LUMO) + 2.54, R2 = 0.793, S.E. = 0.316, F = 71.07, n = 40. A series of equations were obtained about the measured EC50 values of different subclasses of compounds. For those compounds containing double -NO2, their toxicity may be related chiefly to the intracellular reduction of -NO2 obtaining electron, while for anilines and phenols, K(OW) contributes most to the QSAR and E(LUMO) very little.

QSAR Studies of Compounds Acting by Polar and Non‐polar Narcosis: an Examination of the Role of Polarisability and Hydrogen Bonding

The toxicities of 33 non-polar narcotics and 15 polar narcotics have been correlated with the logarithm of the octanol-water partition coefficient (log P). Correlations have also been obtained of toxicities with polarisabilities (α) and free energy hydrogen bond acceptor factors (Ca) calculated using HYBOT-PLUS. There are clear differences in the way non-polar and polar narcotics correlate with log P and with α and Ca, indicating that the two classes of compound exert their toxicity by somewhat different mechanisms.

Quantitative structure-activity relationships of nitroaromatic compounds to four aquatic organisms☆

Abstract Quantitative structure-activity relationships of 26 nitroaromatic compounds to guppy ( Poecilia reticulata ), carp ( Cyprinus carpio), Scenedesmus obliguus, Daphnia carinata were studied based on equations we established. Results showed that observed toxicity of chemicals could be estimated by the parameters of halfwave reduction potential ( E 1 2 ) and bioconcentration factor (BCF). The toxicity data of nitroaromatic compounds to four aquatic organisms were estimated by these parameters. Compared with octanol/water partition coefficient method, the LC 50 values predicted by the two parameters are close to observed LC 50 values. Regression results also showed that the highest occupied molecular orbital energy (E HOMO ), the lowest unoccupied molecular orbital energy (E LUMO ) and octanol/water partition coefficient (K OW ) were ideal parameters instead of the reaction equilibrium constant of target molecule-organic chemical in target cells (K) and bioconcentration factor. Relationships between the toxicity data of guppy, carp, Scenedesmus obliguus, Daphnia carinata and the parameters of E HOMO , E LUMO and K OW were analyzed. Predicted and observed LC 50 values are in good agreement. The observed toxicity data of 2,4-dinitrotoluene and 2,6-dinitrotoluene may be lower than the expected toxicity data because the photolysis of the two chemicals is rapid during the course of experiments.

Evaluation of joint toxicity of nitroaromatic compounds and copper to Photobacterium phosphoreum and QSAR analysis

The individual toxicities of Cu and 11 nitroaromatic compounds to Photobacterium phosphoreum were determined. The toxicity was expressed as the concentrations causing a 50% inhibition of bioluminescence after 15 min exposure (IC(50)). To evaluate the joint effect between the metal ion and the 11 nitroaromatic compounds, the joint toxicity of Cu and 11 nitroaromatic compounds were measured at different Cu concentrations (0.2IC(50), 0.5IC(50) and 0.8IC(50)), respectively. The result shows that the binary joint effect between Cu and nitroaromatic compounds is mainly simple addition at the low Cu concentration (0.2IC(50)). However, an antagonism effect, 55% and 64%, was observed between Cu and 11 nitroaromatic compounds for Cu at medium and high concentrations (0.5IC(50) and 0.8IC(50)). Quantitative structure-activity relationship (QSAR) analysis was performed to study the joint toxicity for the 11 nitroaromatic compounds. The result shows that the toxicity of nitroaromatic compounds is related to descriptors of Connolly solvent-excluded volume (CSEV) and dipolarity/polarizability (S) at low Cu concentration. On the other hand, the toxicity is related to Connolly accessible area (CAA) at medium and high Cu concentrations. The result indicates that different QSAR models on complex mixtures need to be developed to assess the ecological risk in real environments. Using single toxic data to evaluate the toxic effect of mixtures may result in wrong conclusions.

Discrimination of excess toxicity from narcotic effect: Comparison of toxicity of class-based organic chemicals to Daphnia magna and Tetrahymena pyriformis

The discrimination of excess toxicity from narcotic effect plays a crucial role in the study of modes of toxic action for organic compounds. In this paper, the toxicity data of 758 chemicals to Daphnia magna and 993 chemicals to Tetrahymena pyriformis were used to investigate the excess toxicity. The result showed that mode of toxic action of chemicals is species dependent. The toxic ratio (TR) calculated from baseline model over the experimentally determined values showed that some classes (e.g. alkanes, alcohols, ethers, aldehydes, esters and benzenes) shared same modes of toxic action to both D. magna and T. pyriformis. However, some classes may share different modes of toxic action to T. pyriformis and D. magna (e.g. anilines and their derivatives). For the interspecies comparison, same reference threshold need to be used between species toxicity. The excess toxicity indicates that toxicity enhancement is driven by reactive or specific toxicity. However, not all the reactive compounds exhibit excess toxicity. In theory, the TR threshold should not be related with the experimental uncertainty. The experimental uncertainty only brings the difficulty for discriminating the toxic category of chemicals. The real threshold of excess toxicity which is used to identify baseline from reactive chemicals should be based on the critical concentration difference inside body, rather than critical concentration outside body (i.e. EC50 or IGC50). The experimental bioconcentration factors can be greatly different from predicted bioconcentration factors, resulting in different toxic ratios and leading to mis-classification of toxic category and outliers.

Effects of Atmospheric Water on ·OH-initiated Oxidation of Organophosphate Flame Retardants: A DFT Investigation on TCPP

Tris(2-chloroisopropyl) phosphate (TCPP), a widely used organophosphate flame retardant, has been recognized as an important atmospheric pollutant. It is notable that TCPP has potential for long-range atmospheric transport. However, its atmospheric fate is unknown, restricting its environmental risk assessment. Herein we performed quantum chemical calculations to investigate the atmospheric transformation mechanisms and kinetics of TCPP initiated by ·OH in the presence of O2/NO/NO2, and the effects of ubiquitous water on these reactions. Results show the H-abstraction pathways are the most favorable for the titled reaction. The calculated gaseous rate constant and lifetime at 298 K are 1.7 × 10-10 cm3molecule-1 s-1 and 1.7 h, respectively. However, when considering atmospheric water, the corresponding lifetime is about 0.5-20.2 days. This study reveals for the first time that water has a negative role in the ·OH-initiated degradation of TCPP by modifying the stabilities of prereactive complexes and transition states via forming hydrogen bonds, which unveils one underlying mechanism for the observed persistence of TCPP in the atmosphere. Water also influences secondary reaction pathways of selected TCPP radicals formed from the primary H-abstraction. These results demonstrate the importance of water in the evaluation of the atmospheric fate of newly synthesized chemicals and emerging pollutants.

Evaluation of Combined Toxicity of Phenols and Lead to Photobacterium phosphoreum and Quantitative Structure–Activity Relationships

The combined toxicity of lead (Pb) and nine phenols were measured. The result indicated that the combined toxicity is not only dependent on the Pb concentrations but also on the positions of substituted groups of phenols. Quantitative structure–activity relationship equations were built from the combined toxicity and physico-chemical descriptors of phenols in the different Pb concentrations. The combined toxicity was related to water solubility and the third order molecular connectivity index (3X) in low Pb concentration, to solute excess molar refractivity (E) and ionization constant (pKa) in medium Pb concentration and to dipolarity/polarizability (S) in high Pb concentration.

Investigation on the relationship between critical body residue and bioconcentration in zebrafish based on bio-uptake kinetics for five nitro-aromatics

It is well known that the critical body residue (CBR) can be estimated via bioconcentration factor (BCF). However, the relationship between CBR and BCF in zebrafish has not been carried out based on bio-uptake kinetics for nitro-aromatics. In this paper, the time-variable concentrations and CBRs in zebrafish were determined for five nitro substituted benzenes. The result shows that CBR values can well be calculated from the BCF and external critical concentrations (LC50). Although CBRs measured from 5 h exposure period are greater than the CBRs obtained from 96 h for the five nitro-aromatics, no significant difference was observed, indicating that the CBR approach is a truer measure of chemical levels in exposed organisms and an ideal indicator to reflect the toxicity of a chemical. The bio-uptake can well be described by first-order kinetics and reach steady-state within 48 h. Almost same BCF values are obtained from the ratio of concentration in the fish (Cf) and in the water (Cw) at apparent steady-state and the ratio of the rate constants of uptake (k1) and depuration (k2) assuming first-order kinetics. The toxicity ratio (TR) can reflect the difference of internal critical concentrations and be used to identify mode of action.

Aqueous OH Radical Reaction Rate Constants for Organophosphorus Flame Retardants and Plasticizers: Experimental and Modeling Studies

Aqueous ·OH reaction rate constants ( kOH) for organophosphate esters (OPEs) are essential for assessing their environmental fate and removal potential in advanced oxidation processes (AOPs). Herein experimental and in silico approaches were adopted to obtain kOH values for a variety of OPEs. The determined kOH for 18 OPEs varies from 4.0 × 108 M-1 s-1 to 1.6 × 1010 M-1 s-1. Based on the experimental kOH values, a quantitative structure-activity relationship model that involves molecular structural information on the number of heavy atoms, content index, and the most negative charge of C atoms was developed for predicting kOH of other OPEs. Furthermore, appropriate density functional theory (DFT) and solvation models were selected, which together with transition state theory were employed to predict kOH of three representative OPEs. The deviation between the DFT calculated and the experimental kOH values ( kcal/ kexp) is within 2. Half-lives of the OPEs were estimated to be 0.5-22791.3 days in natural waters and 0.044-19.7 s in AOPs, indicating the OPEs are potentially persistent in natural waters and can be quickly eliminated by AOPs. The determined kOH values and the in silico methods offer a scientific base for assessing OPEs fate in aquatic environments.