Percutaneous penetration of typical Organophosphate esters under catalysis by Carboxylesterase: Characteristics, mechanism and prediction model
Although the relationship between organophosphate esters (OPEs) percutaneous penetration and their specific physicochemical properties has been investigated, little information is available regarding the percutaneous penetration of OPEs under the interaction of skin enzymes. Herein, we used an in vi...
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Elsevier
2025-04-01
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| Series: | Environment International |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0160412025001709 |
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| author | Yan Yang Yuwan Hou Yonglong Liao Zeji Huang Jiejie Pan Xin Yang Haojia Chen Zenghua Qi |
| author_facet | Yan Yang Yuwan Hou Yonglong Liao Zeji Huang Jiejie Pan Xin Yang Haojia Chen Zenghua Qi |
| author_sort | Yan Yang |
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| description | Although the relationship between organophosphate esters (OPEs) percutaneous penetration and their specific physicochemical properties has been investigated, little information is available regarding the percutaneous penetration of OPEs under the interaction of skin enzymes. Herein, we used an in vitro skin model to quantitatively assess the skin permeation of six typical OPEs. The in vitro results demonstrated that 0.34–49.87% of OPEs and 0.80–2.95% of their metabolites (mOPEs) penetrated the skin. Notably, triphenyl phosphate (TPHP) and tri-3-cresyl phosphate (TCRP), which exhibit high lipophilicity and large molecular weights, were more likely to be deposited in the skin tissue, thereby hindering their penetration into the body. However, the concentrations of their metabolites, diphenyl hydrogen phosphate (DPHP) and bis(2-methylphenoxy) phosphinic acid (DCRP), in the receptor fluid were approximately six times higher than those of their parent compounds. After in vivo dermal OPE exposure, all parent OPEs were detected in both the stratum corneum and viable tissue (VT). Proteomic analysis and enzymatic hydrolysis experiments revealed that the percutaneous biotransformation of OPEs in VT is mediated primarily by carboxylesterase (CES). A biomimetic bilayer skin membrane based on the CES level in fresh skin yielded results closer to the real skin absorption data of OPEs than prior models. Thus, a more accurate prediction model was established to assess the percutaneous penetration of OPEs. Our results provide valuable insights into the skin absorption of OPEs and emphasize the role of skin CES in calculating and predicting the percutaneous penetration of OPEs. |
| format | Article |
| id | doaj-art-53f1ec6319ae4a9896e601e49680d4cc |
| institution | OA Journals |
| issn | 0160-4120 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Elsevier |
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| series | Environment International |
| spelling | doaj-art-53f1ec6319ae4a9896e601e49680d4cc2025-08-20T02:24:58ZengElsevierEnvironment International0160-41202025-04-0119810941910.1016/j.envint.2025.109419Percutaneous penetration of typical Organophosphate esters under catalysis by Carboxylesterase: Characteristics, mechanism and prediction modelYan Yang0Yuwan Hou1Yonglong Liao2Zeji Huang3Jiejie Pan4Xin Yang5Haojia Chen6Zenghua Qi7School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou 510006, China; Synergy Innovation Institute of Guangdong University of Technology, Shantou 515041, ChinaSchool of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou 510006, China; Synergy Innovation Institute of Guangdong University of Technology, Shantou 515041, ChinaSchool of Environmental Science and Engineering, Guangdong University of Technology, Guangzhou 510006, China; Synergy Innovation Institute of Guangdong University of Technology, Shantou 515041, ChinaSchool of Environmental Science and Engineering, Guangdong University of Technology, Guangzhou 510006, China; Synergy Innovation Institute of Guangdong University of Technology, Shantou 515041, ChinaSchool of Environmental Science and Engineering, Guangdong University of Technology, Guangzhou 510006, ChinaSchool of Environmental Science and Engineering, Guangdong University of Technology, Guangzhou 510006, China; Synergy Innovation Institute of Guangdong University of Technology, Shantou 515041, ChinaSchool of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou 510006, China; Synergy Innovation Institute of Guangdong University of Technology, Shantou 515041, ChinaSchool of Environmental Science and Engineering, Guangdong University of Technology, Guangzhou 510006, China; Corresponding author.Although the relationship between organophosphate esters (OPEs) percutaneous penetration and their specific physicochemical properties has been investigated, little information is available regarding the percutaneous penetration of OPEs under the interaction of skin enzymes. Herein, we used an in vitro skin model to quantitatively assess the skin permeation of six typical OPEs. The in vitro results demonstrated that 0.34–49.87% of OPEs and 0.80–2.95% of their metabolites (mOPEs) penetrated the skin. Notably, triphenyl phosphate (TPHP) and tri-3-cresyl phosphate (TCRP), which exhibit high lipophilicity and large molecular weights, were more likely to be deposited in the skin tissue, thereby hindering their penetration into the body. However, the concentrations of their metabolites, diphenyl hydrogen phosphate (DPHP) and bis(2-methylphenoxy) phosphinic acid (DCRP), in the receptor fluid were approximately six times higher than those of their parent compounds. After in vivo dermal OPE exposure, all parent OPEs were detected in both the stratum corneum and viable tissue (VT). Proteomic analysis and enzymatic hydrolysis experiments revealed that the percutaneous biotransformation of OPEs in VT is mediated primarily by carboxylesterase (CES). A biomimetic bilayer skin membrane based on the CES level in fresh skin yielded results closer to the real skin absorption data of OPEs than prior models. Thus, a more accurate prediction model was established to assess the percutaneous penetration of OPEs. Our results provide valuable insights into the skin absorption of OPEs and emphasize the role of skin CES in calculating and predicting the percutaneous penetration of OPEs.http://www.sciencedirect.com/science/article/pii/S0160412025001709Organophosphate estersPercutaneous penetrationEnzymolysisCarboxylesterasePrediction model |
| spellingShingle | Yan Yang Yuwan Hou Yonglong Liao Zeji Huang Jiejie Pan Xin Yang Haojia Chen Zenghua Qi Percutaneous penetration of typical Organophosphate esters under catalysis by Carboxylesterase: Characteristics, mechanism and prediction model Environment International Organophosphate esters Percutaneous penetration Enzymolysis Carboxylesterase Prediction model |
| title | Percutaneous penetration of typical Organophosphate esters under catalysis by Carboxylesterase: Characteristics, mechanism and prediction model |
| title_full | Percutaneous penetration of typical Organophosphate esters under catalysis by Carboxylesterase: Characteristics, mechanism and prediction model |
| title_fullStr | Percutaneous penetration of typical Organophosphate esters under catalysis by Carboxylesterase: Characteristics, mechanism and prediction model |
| title_full_unstemmed | Percutaneous penetration of typical Organophosphate esters under catalysis by Carboxylesterase: Characteristics, mechanism and prediction model |
| title_short | Percutaneous penetration of typical Organophosphate esters under catalysis by Carboxylesterase: Characteristics, mechanism and prediction model |
| title_sort | percutaneous penetration of typical organophosphate esters under catalysis by carboxylesterase characteristics mechanism and prediction model |
| topic | Organophosphate esters Percutaneous penetration Enzymolysis Carboxylesterase Prediction model |
| url | http://www.sciencedirect.com/science/article/pii/S0160412025001709 |
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