Physiologically based toxicokinetic modelling of Tri(2-chloroethyl) phosphate (TCEP) in mice accounting for multiple exposure routes
Exposure routes are important for health risk assessment of chemical risks. The application of physiologically based toxicokinetic (PBTK) models to predict concentrations in vivo can determine the effects of harmful substances and tissue accumulation on the premise of saving experimental costs. In t...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-02-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651324000514 |
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| author | Jiaqi Ding Wanyu He Wanxiao Sha Guoqiang Shan Lingyan Zhu Lin Zhu Jianfeng Feng |
| author_facet | Jiaqi Ding Wanyu He Wanxiao Sha Guoqiang Shan Lingyan Zhu Lin Zhu Jianfeng Feng |
| author_sort | Jiaqi Ding |
| collection | DOAJ |
| description | Exposure routes are important for health risk assessment of chemical risks. The application of physiologically based toxicokinetic (PBTK) models to predict concentrations in vivo can determine the effects of harmful substances and tissue accumulation on the premise of saving experimental costs. In this study, Tri(2-chloroethyl) phosphate (TCEP), an organophosphate ester (OPE), was used as an example to study the PBTK model of mice exposed to different exposure doses by multiple routes. Different routes of exposure (gavage and intradermal injection) can cause differences in the concentration of chemicals in the organs. TCEP that enters the body through the mouth is mainly concentrated in the gastrointestinal tract and liver. However, the concentrations of chemicals that enter the skin into the mice are higher in skin, rest of body, and blood. In addition, TCEP was absorbed and accumulated very rapidly in mice, within half an hour after a single exposure. We have successfully established a mouse PBTK model of the TCEP accounting for multiple exposure Routes and obtained a series of kinetic parameters. The model includes blood, liver, kidney, stomach, intestine, skin, and rest of body compartments. Oral and dermal exposure route was considered for PBTK model. The PBTK model established in this study has a good predictive ability. More than 70% of the predicted values deviated from the measured values by less than 5-fold. In addition, we extrapolated the model to humans. A human PBTK model is built. We performed a health risk assessment for world populations based on human PBTK model. The risk of TCEP in dust is greater through mouth than through skin. The risk of TCEP in food of Chinese population is greater than dust. |
| first_indexed | 2024-03-08T06:56:39Z |
| format | Article |
| id | doaj.art-233715699b5c46b7b611100f8285ef91 |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-03-08T06:56:39Z |
| publishDate | 2024-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-233715699b5c46b7b611100f8285ef912024-02-03T06:34:30ZengElsevierEcotoxicology and Environmental Safety0147-65132024-02-01271115976Physiologically based toxicokinetic modelling of Tri(2-chloroethyl) phosphate (TCEP) in mice accounting for multiple exposure routesJiaqi Ding0Wanyu He1Wanxiao Sha2Guoqiang Shan3Lingyan Zhu4Lin Zhu5Jianfeng Feng6Key laboratory of Pollution process and Environmental Criteria of Ministry of Education and Tianjin Key Laboratory of Environmental Technology for Complex Trans-Media Pollution, College of Environmental Science and Engineering, Nankai University, Tianjin 300071, ChinaKey laboratory of Pollution process and Environmental Criteria of Ministry of Education and Tianjin Key Laboratory of Environmental Technology for Complex Trans-Media Pollution, College of Environmental Science and Engineering, Nankai University, Tianjin 300071, ChinaKey laboratory of Pollution process and Environmental Criteria of Ministry of Education and Tianjin Key Laboratory of Environmental Technology for Complex Trans-Media Pollution, College of Environmental Science and Engineering, Nankai University, Tianjin 300071, ChinaKey laboratory of Pollution process and Environmental Criteria of Ministry of Education and Tianjin Key Laboratory of Environmental Technology for Complex Trans-Media Pollution, College of Environmental Science and Engineering, Nankai University, Tianjin 300071, ChinaKey laboratory of Pollution process and Environmental Criteria of Ministry of Education and Tianjin Key Laboratory of Environmental Technology for Complex Trans-Media Pollution, College of Environmental Science and Engineering, Nankai University, Tianjin 300071, ChinaKey laboratory of Pollution process and Environmental Criteria of Ministry of Education and Tianjin Key Laboratory of Environmental Technology for Complex Trans-Media Pollution, College of Environmental Science and Engineering, Nankai University, Tianjin 300071, ChinaCorresponding author.; Key laboratory of Pollution process and Environmental Criteria of Ministry of Education and Tianjin Key Laboratory of Environmental Technology for Complex Trans-Media Pollution, College of Environmental Science and Engineering, Nankai University, Tianjin 300071, ChinaExposure routes are important for health risk assessment of chemical risks. The application of physiologically based toxicokinetic (PBTK) models to predict concentrations in vivo can determine the effects of harmful substances and tissue accumulation on the premise of saving experimental costs. In this study, Tri(2-chloroethyl) phosphate (TCEP), an organophosphate ester (OPE), was used as an example to study the PBTK model of mice exposed to different exposure doses by multiple routes. Different routes of exposure (gavage and intradermal injection) can cause differences in the concentration of chemicals in the organs. TCEP that enters the body through the mouth is mainly concentrated in the gastrointestinal tract and liver. However, the concentrations of chemicals that enter the skin into the mice are higher in skin, rest of body, and blood. In addition, TCEP was absorbed and accumulated very rapidly in mice, within half an hour after a single exposure. We have successfully established a mouse PBTK model of the TCEP accounting for multiple exposure Routes and obtained a series of kinetic parameters. The model includes blood, liver, kidney, stomach, intestine, skin, and rest of body compartments. Oral and dermal exposure route was considered for PBTK model. The PBTK model established in this study has a good predictive ability. More than 70% of the predicted values deviated from the measured values by less than 5-fold. In addition, we extrapolated the model to humans. A human PBTK model is built. We performed a health risk assessment for world populations based on human PBTK model. The risk of TCEP in dust is greater through mouth than through skin. The risk of TCEP in food of Chinese population is greater than dust.http://www.sciencedirect.com/science/article/pii/S0147651324000514TCEPPBTK modelMouseMultiple Exposure Routes |
| spellingShingle | Jiaqi Ding Wanyu He Wanxiao Sha Guoqiang Shan Lingyan Zhu Lin Zhu Jianfeng Feng Physiologically based toxicokinetic modelling of Tri(2-chloroethyl) phosphate (TCEP) in mice accounting for multiple exposure routes Ecotoxicology and Environmental Safety TCEP PBTK model Mouse Multiple Exposure Routes |
| title | Physiologically based toxicokinetic modelling of Tri(2-chloroethyl) phosphate (TCEP) in mice accounting for multiple exposure routes |
| title_full | Physiologically based toxicokinetic modelling of Tri(2-chloroethyl) phosphate (TCEP) in mice accounting for multiple exposure routes |
| title_fullStr | Physiologically based toxicokinetic modelling of Tri(2-chloroethyl) phosphate (TCEP) in mice accounting for multiple exposure routes |
| title_full_unstemmed | Physiologically based toxicokinetic modelling of Tri(2-chloroethyl) phosphate (TCEP) in mice accounting for multiple exposure routes |
| title_short | Physiologically based toxicokinetic modelling of Tri(2-chloroethyl) phosphate (TCEP) in mice accounting for multiple exposure routes |
| title_sort | physiologically based toxicokinetic modelling of tri 2 chloroethyl phosphate tcep in mice accounting for multiple exposure routes |
| topic | TCEP PBTK model Mouse Multiple Exposure Routes |
| url | http://www.sciencedirect.com/science/article/pii/S0147651324000514 |
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