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Author:

Wang, Yutong (Wang, Yutong.) | Wang, Peng (Wang, Peng.) | Fan, Tengjiao (Fan, Tengjiao.) | Ren, Ting (Ren, Ting.) | Zhang, Na (Zhang, Na.) | Zhao, Lijiao (Zhao, Lijiao.) | Zhong, Rugang (Zhong, Rugang.) | Sun, Guohui (Sun, Guohui.)

Indexed by:

EI Scopus SCIE

Abstract:

The escalating introduction of pesticides/veterinary drugs into the environment has necessitated a rapid evaluation of their potential risks to ecosystems and human health. The developmental toxicity of pesticides/veterinary drugs was less explored, and much less the large-scale predictions for untested pesticides, veterinary drugs and bio-pesticides. Alternative methods like quantitative structure-activity relationship (QSAR) are promising because their potential to ensure the sustainable and safe use of these chemicals. We collected 133 pesticides and veterinary drugs with half-maximal active concentration (AC(50)) as the zebrafish embryo developmental toxicity endpoint. The QSAR model development adhered to rigorous OECD principles, ensuring that the model possessed good internal robustness (R-2 > 0.6 and Q(LOO)(2) > 0.6) and external predictivity (R-2 test > 0.7, Q(Fn)(2) >0.7, and CCCtest > 0.85). To further enhance the predictive performance of the model, a quantitative readacross structure-activity relationship (q-RASAR) model was established using the combined set of RASAR and 2D descriptors. Mechanistic interpretation revealed that dipole moment, the presence of C-O fragment at 10 topological distance, molecular size, lipophilicity, and Euclidean distance (ED)-based RA function were main factors influencing toxicity. For the first time, the established QSAR and q-RASAR models were combined to prioritize the developmental toxicity of a vast array of true external compounds (pesticides/veterinary drugs/bio-pesticides) lacking experimental values. The prediction reliability of each query molecule was evaluated by leverage approach and prediction reliability indicator. Overall, the dual computational toxicology models can inform decision-making and guide the design of new pesticides/veterinary drugs with improved safety profiles.

Keyword:

Q-RASAR QSAR Veterinary drugs (Bio)Pesticides Embryonic developmental toxicity

Author Community:

  • [ 1 ] [Wang, Yutong]Beijing Univ Technol, Coll Chem & Life Sci, Beijing Key Lab Environm & Viral Oncol, Beijing 100124, Peoples R China
  • [ 2 ] [Fan, Tengjiao]Beijing Univ Technol, Coll Chem & Life Sci, Beijing Key Lab Environm & Viral Oncol, Beijing 100124, Peoples R China
  • [ 3 ] [Ren, Ting]Beijing Univ Technol, Coll Chem & Life Sci, Beijing Key Lab Environm & Viral Oncol, Beijing 100124, Peoples R China
  • [ 4 ] [Zhang, Na]Beijing Univ Technol, Coll Chem & Life Sci, Beijing Key Lab Environm & Viral Oncol, Beijing 100124, Peoples R China
  • [ 5 ] [Zhao, Lijiao]Beijing Univ Technol, Coll Chem & Life Sci, Beijing Key Lab Environm & Viral Oncol, Beijing 100124, Peoples R China
  • [ 6 ] [Zhong, Rugang]Beijing Univ Technol, Coll Chem & Life Sci, Beijing Key Lab Environm & Viral Oncol, Beijing 100124, Peoples R China
  • [ 7 ] [Sun, Guohui]Beijing Univ Technol, Coll Chem & Life Sci, Beijing Key Lab Environm & Viral Oncol, Beijing 100124, Peoples R China
  • [ 8 ] [Wang, Peng]Chinese Peoples Liberat Army Gen Hosp, Med Ctr 1, Dept Neurosurg, Beijing 100853, Peoples R China
  • [ 9 ] [Fan, Tengjiao]Beijing Pharmaceut Univ, Dept Med Technol, Beijing 100079, Peoples R China

Reprint Author's Address:

  • [Sun, Guohui]Beijing Univ Technol, Coll Chem & Life Sci, Beijing Key Lab Environm & Viral Oncol, Beijing 100124, Peoples R China;;

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Source :

JOURNAL OF HAZARDOUS MATERIALS

ISSN: 0304-3894

Year: 2024

Volume: 476

1 3 . 6 0 0

JCR@2022

Cited Count:

WoS CC Cited Count:

SCOPUS Cited Count:

ESI Highly Cited Papers on the List: 0 Unfold All

WanFang Cited Count:

Chinese Cited Count:

30 Days PV: 1

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