Advancing Chemical Risk Assessment through Human Physiology-Based Biochemical Process Modeling
Physiology-Based BioKinetic (PBBK) models are of increasing interest in modern risk assessment, providing quantitative information regarding the absorption, metabolism, distribution, and excretion (ADME). They focus on the estimation of the effective dose at target sites, aiming at the identificatio...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-01-01
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| Series: | Fluids |
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| Online Access: | http://www.mdpi.com/2311-5521/4/1/4 |
| _version_ | 1818175094302703616 |
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| author | Dimosthenis Sarigiannis Spyros Karakitsios |
| author_facet | Dimosthenis Sarigiannis Spyros Karakitsios |
| author_sort | Dimosthenis Sarigiannis |
| collection | DOAJ |
| description | Physiology-Based BioKinetic (PBBK) models are of increasing interest in modern risk assessment, providing quantitative information regarding the absorption, metabolism, distribution, and excretion (ADME). They focus on the estimation of the effective dose at target sites, aiming at the identification of xenobiotic levels that are able to result in perturbations to the biological pathway that are potentially associated with adverse outcomes. The current study aims at the development of a lifetime PBBK model that covers a large chemical space, coupled with a framework for human biomonitoring (HBM) data assimilation. The methodology developed herein was demonstrated in the case of bisphenol A (BPA), where exposure analysis was based on European HBM data. Based on our calculations, it was found that current exposure levels in Europe are below the temporary Tolerable Daily Intake (t-TDI) of 4 μg/kg_bw/day proposed by the European Food Safety Authority (EFSA). Taking into account age-dependent bioavailability differences, internal exposure was estimated and compared with the biologically effective dose (BED) resulting from translating the EFSA temporary total daily intake (t-TDI) into equivalent internal dose and an alternative internal exposure reference value, namely biological pathway altering dose (BPAD); the use of such a refined exposure metric, showed that environmentally relevant exposure levels are below the concentrations associated with the activation of biological pathways relevant to toxicity based on High Throughput Screening (HTS) in vitro studies. |
| first_indexed | 2024-12-11T19:54:50Z |
| format | Article |
| id | doaj.art-aa46a98a17704c9f87f3097f20a014b9 |
| institution | Directory Open Access Journal |
| issn | 2311-5521 |
| language | English |
| last_indexed | 2024-12-11T19:54:50Z |
| publishDate | 2019-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Fluids |
| spelling | doaj.art-aa46a98a17704c9f87f3097f20a014b92022-12-22T00:52:40ZengMDPI AGFluids2311-55212019-01-0141410.3390/fluids4010004fluids4010004Advancing Chemical Risk Assessment through Human Physiology-Based Biochemical Process ModelingDimosthenis Sarigiannis0Spyros Karakitsios1HERACLES Research Center on the Exposome and Health, Center for Interdisciplinary Research and Innovation, Balkan Center, Bldg. B, 10th km Thessaloniki-Thermi Road, 57001 Thermi, GreeceHERACLES Research Center on the Exposome and Health, Center for Interdisciplinary Research and Innovation, Balkan Center, Bldg. B, 10th km Thessaloniki-Thermi Road, 57001 Thermi, GreecePhysiology-Based BioKinetic (PBBK) models are of increasing interest in modern risk assessment, providing quantitative information regarding the absorption, metabolism, distribution, and excretion (ADME). They focus on the estimation of the effective dose at target sites, aiming at the identification of xenobiotic levels that are able to result in perturbations to the biological pathway that are potentially associated with adverse outcomes. The current study aims at the development of a lifetime PBBK model that covers a large chemical space, coupled with a framework for human biomonitoring (HBM) data assimilation. The methodology developed herein was demonstrated in the case of bisphenol A (BPA), where exposure analysis was based on European HBM data. Based on our calculations, it was found that current exposure levels in Europe are below the temporary Tolerable Daily Intake (t-TDI) of 4 μg/kg_bw/day proposed by the European Food Safety Authority (EFSA). Taking into account age-dependent bioavailability differences, internal exposure was estimated and compared with the biologically effective dose (BED) resulting from translating the EFSA temporary total daily intake (t-TDI) into equivalent internal dose and an alternative internal exposure reference value, namely biological pathway altering dose (BPAD); the use of such a refined exposure metric, showed that environmentally relevant exposure levels are below the concentrations associated with the activation of biological pathways relevant to toxicity based on High Throughput Screening (HTS) in vitro studies.http://www.mdpi.com/2311-5521/4/1/4biochemical processesbiokineticshuman biomonitoringbisphenol Aexposure reconstructionrisk assessment |
| spellingShingle | Dimosthenis Sarigiannis Spyros Karakitsios Advancing Chemical Risk Assessment through Human Physiology-Based Biochemical Process Modeling Fluids biochemical processes biokinetics human biomonitoring bisphenol A exposure reconstruction risk assessment |
| title | Advancing Chemical Risk Assessment through Human Physiology-Based Biochemical Process Modeling |
| title_full | Advancing Chemical Risk Assessment through Human Physiology-Based Biochemical Process Modeling |
| title_fullStr | Advancing Chemical Risk Assessment through Human Physiology-Based Biochemical Process Modeling |
| title_full_unstemmed | Advancing Chemical Risk Assessment through Human Physiology-Based Biochemical Process Modeling |
| title_short | Advancing Chemical Risk Assessment through Human Physiology-Based Biochemical Process Modeling |
| title_sort | advancing chemical risk assessment through human physiology based biochemical process modeling |
| topic | biochemical processes biokinetics human biomonitoring bisphenol A exposure reconstruction risk assessment |
| url | http://www.mdpi.com/2311-5521/4/1/4 |
| work_keys_str_mv | AT dimosthenissarigiannis advancingchemicalriskassessmentthroughhumanphysiologybasedbiochemicalprocessmodeling AT spyroskarakitsios advancingchemicalriskassessmentthroughhumanphysiologybasedbiochemicalprocessmodeling |