Stereoselective Toxicokinetic and Distribution Study on the Hexaconazole Enantiomers in Mice

Hexaconazole (Hex) has been widely used in agricultural products, and its residues may pose a potential risk to human health. However, the metabolic behavior of Hex enantiomers in mammal organisms is still unknown, which is important for evaluating the differences in their toxicity. In this study, the distribution of S-(+)- and R-(−)-Hex in mice was detected by an ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UPLC–MS/MS), and the mechanism differences in the toxicokinetic behavior were analyzed by molecular docking. Good linearities, accuracies, and precisions were achieved for S-(+)- and R-(−)-Hex, with recoveries of 88.7~104.2% and RSDs less than 9.45% in nine tissues of mice. This established method was then used to detect the toxicokinetic of Hex enantiomers in mice after oral administration within 96 h. The results showed that the half-lives of S-(+)- and R-(−)-Hex were 3.07 and 3.71 h in plasma. Hex was mainly accumulated in the liver, followed by the kidneys, brain, lungs, spleen, and heart. The enantiomeric fraction (EF) values of Hex enantiomers in most of the samples were below 1, indicating that S-(+)-Hex decreased faster than its antipode. The molecular docking showed that the binding of S-(+)-Hex with P450arom was much more stable than R-(−)-Hex, which verified the fact that S-(+)-Hex was prefer to decrease in most of the tissues. The results of this study could be helpful for further evaluating the potential toxic risk of Hex enantiomers and for the development and usage of its pure monomer

Fractional biharmonic operator equation model for arbitrary frequency-dependent scattering attenuation in acoustic wave propagation

This paper proposes a fractional biharmonic operator equation model in the time-space domain to describe scattering attenuation of acoustic waves in heterogeneous media. Compared with the existing models, the proposed fractional model is able to describe arbitrary frequency-dependent scattering attenuation, which typically obeys an empirical power law with an exponent ranging from 0 to 4. In stark contrast to an extensive and rapidly increasing application of the fractional derivative models for wave absorption attenuation in the literature, little has been reported on frequency-dependent scattering attenuation. This is largely because the order of the fractional Laplacian is from 0 to 2 and is infeasible for scattering attenuation. In this study, the definition of the fractional biharmonic operator in space with an order varying from 0 to 4 is proposed, as well as a fractional biharmonic operator equation model of scattering attenuation which is consistent with arbitrary frequency power-law dependency and obeys the causal relation under the smallness approximation. Finally, the correlation between the fractional order and the ratio of wavelength to the diameter of the scattering heterogeneity is investigated and an expression on exponential form is also provided. © 2017 Acoustical Society of Americ