Yan Yang , Yuwan Hou , Yonglong Liao , Zeji Huang , Jiejie Pan , Xin Yang , Haojia Chen , Zenghua Qi
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引用次数: 0
Abstract
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.
期刊介绍:
Environmental Health publishes manuscripts focusing on critical aspects of environmental and occupational medicine, including studies in toxicology and epidemiology, to illuminate the human health implications of exposure to environmental hazards. The journal adopts an open-access model and practices open peer review.
It caters to scientists and practitioners across all environmental science domains, directly or indirectly impacting human health and well-being. With a commitment to enhancing the prevention of environmentally-related health risks, Environmental Health serves as a public health journal for the community and scientists engaged in matters of public health significance concerning the environment.