Leveraging New Approach Methodologies: Ecotoxicological Modelling of Endocrine Disrupting Chemicals to Danio rerio through Machine Learning and Toxicity Studies

Toxicology Mechanisms and Methods, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 17

Published: Sept. 3, 2024

Emerging endocrine-disrupting chemicals (EDCs) are a diverse group of toxic substances that disrupt the endocrine system. These can only be approved after obtaining concrete evidence their toxicity. New approach methodologies (NAMs) offer information tailored to intended application while reducing use animals. NAMs aim develop quantitative structure-activity relationship (QSAR) and quantitive-Read-Across (q-RASAR) models predict categorize acute toxicity known unknown EDCs. The q-RASAR model was constructed verified using validation metrics (R2 = 0.886 Q2 0.814). substructure fingerprint well-fitted for classification validated 10-fold average accuracy (Q 86.88%), specificity (Sp 88.89%), Matthew's correlation curve (MCC 0.621) receiver operating characteristics (ROC 0.828). dataset revealed phenolphthalein (Php) exhibited significant level docking simulation study results indicated computationally derived important features successfully bound target zebrafish sex hormone binding globulin (zfSHBG). experimental LC50 value 0.790 mg L−1 very close predicted 0.763 L−1, which provides high confidence developed model.

Language: Английский

Development and Application of a New QuEChERS Method Coupled with UPLC-QTOF-MS/MS for Analysis of Tiafenacil and Its Photolysis Products in Water

Journal of Agricultural and Food Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 19, 2024

This research centered on the novel pyrimidinedione herbicide, tiafenacil. Residues of tiafenacil and its three photolysis products (PP1 to PP3) in water were analyzed using advanced QuEChERS UPLC-QTOF-MS/MS techniques, reaching a low limit quantitation (LOQ) 10 μg/L. Calibration curves exhibited high degree linearity (R2 ≥ 0.993) over concentration range 0.01 1.00 mg/L. Method validation demonstrated precision, with intraday relative standard deviation RSDr ≤7.9% interday RSDR ≤ 6.1%, along accuracy (recoveries from 94.4% 105.0%). Using density functional theory (DFT) at B3LYP/6-311g (d) level, we calculated electronic properties PPs PP3). Additionally, frontier molecular orbital (FMO) fukui function analyses conducted explore HOMO–LUMO energies, determine energy band gaps for these substances, predict reactive sites their electrophilic, nucleophilic, radical reactions. Significantly, ecotoxicity assessment, including ECOSAR predictions acute toxicity tests, revealed that higher aquatic organisms than Field experiments showed half-life 18.9 days water, fitting first-order kinetic model = 0.999), degradation 41.5% after 14 approximately 89.2% 60 days. study significantly advances our understanding tiafenacil's environmental fate, evaluates associated risks, offers valuable insights responsible application.

Language: Английский