In Vitro Toxicity Screening of Fifty Complex Mixtures in HepG2 Cells
To develop the risk prediction technology for mixture toxicity, a reliable and extensive dataset of experimental results is required. However, most published literature only provides data on combinations containing two or three substances, resulting in a limited dataset for predicting the toxicity o...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-02-01
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| Series: | Toxics |
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| Online Access: | https://www.mdpi.com/2305-6304/12/2/126 |
| _version_ | 1797296971804835840 |
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| author | Sunmi Kim Kyounghee Kang Haena Kim Myungwon Seo |
| author_facet | Sunmi Kim Kyounghee Kang Haena Kim Myungwon Seo |
| author_sort | Sunmi Kim |
| collection | DOAJ |
| description | To develop the risk prediction technology for mixture toxicity, a reliable and extensive dataset of experimental results is required. However, most published literature only provides data on combinations containing two or three substances, resulting in a limited dataset for predicting the toxicity of complex mixtures. Complex mixtures may have different mode of actions (MoAs) due to their varied composition, posing difficulty in the prediction using conventional toxicity prediction models, such as the concentration addition (CA) and independent action (IA) models. The aim of this study was to generate an experimental dataset comprising complex mixtures. To identify the target complex mixtures, we referred to the findings of the HBM4EU project. We identified three groups of seven to ten components that were commonly detected together in human bodies, namely environmental phenols, perfluorinated compounds, and heavy metal compounds, assuming these chemicals to have different MoAs. In addition, a separate mixture was added consisting of seven organophosphate flame retardants (OPFRs), which may have similar chemical structures. All target substances were tested for cytotoxicity using HepG2 cell lines, and subsequently 50 different complex mixtures were randomly generated with equitoxic mixtures of EC10 levels. To determine the interaction effect, we calculated the model deviation ratio (MDR) by comparing the observed EC10 with the predicted EC10 from the CA model, then categorized three types of interactions: antagonism, additivity, and synergism. Dose–response curves and EC values were calculated for all complex mixtures. Out of 50 mixtures, none demonstrated synergism, while six mixtures exhibited an antagonistic effect. The remaining mixtures exhibited additivity with MDRs ranging from 0.50 to 1.34. Our experimental data have been formatted to and constructed for the database. They will be utilized for further research aimed at developing the combined CA/IA approaches to support mixture risk assessment. |
| first_indexed | 2024-03-07T22:12:33Z |
| format | Article |
| id | doaj.art-ea581084bae14c9fa11137de3c5a3f2e |
| institution | Directory Open Access Journal |
| issn | 2305-6304 |
| language | English |
| last_indexed | 2024-03-07T22:12:33Z |
| publishDate | 2024-02-01 |
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| series | Toxics |
| spelling | doaj.art-ea581084bae14c9fa11137de3c5a3f2e2024-02-23T15:36:23ZengMDPI AGToxics2305-63042024-02-0112212610.3390/toxics12020126In Vitro Toxicity Screening of Fifty Complex Mixtures in HepG2 CellsSunmi Kim0Kyounghee Kang1Haena Kim2Myungwon Seo3Chemical Analysis Center, Korea Institute of Chemical Technology (KRICT), Daejeon 34114, Republic of KoreaChemical Analysis Center, Korea Institute of Chemical Technology (KRICT), Daejeon 34114, Republic of KoreaChemical Analysis Center, Korea Institute of Chemical Technology (KRICT), Daejeon 34114, Republic of KoreaChemical Analysis Center, Korea Institute of Chemical Technology (KRICT), Daejeon 34114, Republic of KoreaTo develop the risk prediction technology for mixture toxicity, a reliable and extensive dataset of experimental results is required. However, most published literature only provides data on combinations containing two or three substances, resulting in a limited dataset for predicting the toxicity of complex mixtures. Complex mixtures may have different mode of actions (MoAs) due to their varied composition, posing difficulty in the prediction using conventional toxicity prediction models, such as the concentration addition (CA) and independent action (IA) models. The aim of this study was to generate an experimental dataset comprising complex mixtures. To identify the target complex mixtures, we referred to the findings of the HBM4EU project. We identified three groups of seven to ten components that were commonly detected together in human bodies, namely environmental phenols, perfluorinated compounds, and heavy metal compounds, assuming these chemicals to have different MoAs. In addition, a separate mixture was added consisting of seven organophosphate flame retardants (OPFRs), which may have similar chemical structures. All target substances were tested for cytotoxicity using HepG2 cell lines, and subsequently 50 different complex mixtures were randomly generated with equitoxic mixtures of EC10 levels. To determine the interaction effect, we calculated the model deviation ratio (MDR) by comparing the observed EC10 with the predicted EC10 from the CA model, then categorized three types of interactions: antagonism, additivity, and synergism. Dose–response curves and EC values were calculated for all complex mixtures. Out of 50 mixtures, none demonstrated synergism, while six mixtures exhibited an antagonistic effect. The remaining mixtures exhibited additivity with MDRs ranging from 0.50 to 1.34. Our experimental data have been formatted to and constructed for the database. They will be utilized for further research aimed at developing the combined CA/IA approaches to support mixture risk assessment.https://www.mdpi.com/2305-6304/12/2/126complex mixturecytotoxicitymixture toxicity predictionHepG2biomonitoring |
| spellingShingle | Sunmi Kim Kyounghee Kang Haena Kim Myungwon Seo In Vitro Toxicity Screening of Fifty Complex Mixtures in HepG2 Cells Toxics complex mixture cytotoxicity mixture toxicity prediction HepG2 biomonitoring |
| title | In Vitro Toxicity Screening of Fifty Complex Mixtures in HepG2 Cells |
| title_full | In Vitro Toxicity Screening of Fifty Complex Mixtures in HepG2 Cells |
| title_fullStr | In Vitro Toxicity Screening of Fifty Complex Mixtures in HepG2 Cells |
| title_full_unstemmed | In Vitro Toxicity Screening of Fifty Complex Mixtures in HepG2 Cells |
| title_short | In Vitro Toxicity Screening of Fifty Complex Mixtures in HepG2 Cells |
| title_sort | in vitro toxicity screening of fifty complex mixtures in hepg2 cells |
| topic | complex mixture cytotoxicity mixture toxicity prediction HepG2 biomonitoring |
| url | https://www.mdpi.com/2305-6304/12/2/126 |
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