A comprehensive characterization biotransformation of chlorinated paraffin by human and carp liver microsomes via liquid chromatography-high-resolution mass spectrometry and screening algorithm
The chlorinated paraffin (CP) monomer 1,2,5,6,9,10-Hexachlorodecane (CP-4) was subjected to in vitro biotransformation using human and carp liver microsomes. Five types of CP-4 metabolites (OH–, keto-, enol-, aldehyde- and carboxy-CP-4) were identified in human liver microsomer while only mono-OH-CP...
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Elsevier
2025-01-01
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| Series: | Environment International |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0160412024008225 |
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| author | Liujun Chen Caiming Tang Zhiqiang Yu Yanhong Zeng Bixian Mai Xiaojun Luo |
| author_facet | Liujun Chen Caiming Tang Zhiqiang Yu Yanhong Zeng Bixian Mai Xiaojun Luo |
| author_sort | Liujun Chen |
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| description | The chlorinated paraffin (CP) monomer 1,2,5,6,9,10-Hexachlorodecane (CP-4) was subjected to in vitro biotransformation using human and carp liver microsomes. Five types of CP-4 metabolites (OH–, keto-, enol-, aldehyde- and carboxy-CP-4) were identified in human liver microsomer while only mono-OH-CP-4 was found in the carp liver microsomes. Kinetic studies revealed that the formation of mono-, di-, tri-hydroxylated CP-4, keto-, enol-, and aldehyde-CP-4 in human liver microsomes was best described by substrate inhibition models, whereas the formation of carboxylated CP-4 metabolites best fit the Michaelis–Menten model. Notably, keto-CP-4, enol-CP-4 and aldehyde-CP-4 were the predominant metabolites. The estimated Vmax values for these metabolites were significantly higher in the human liver microsomes than in the carp liver microsomes. The intrinsic hepatic clearance (CLint) of CP-4 was higher in humans than in carp, indicating species-specific differences in its metabolism. This study also highlighted potential toxicity concerns, with computational predictions showing varying degrees of acute oral toxicity for CP-4 and its metabolites. These findings indicate significant species-specific differences in the biotransformation of CP-4, emphasizing the potential health and environmental risks associated with chlorinated paraffins and their metabolites, and underscore the need for further research to address these concerns. |
| format | Article |
| id | doaj-art-95591020b3be4b90931dc744376dd30c |
| institution | Kabale University |
| issn | 0160-4120 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Environment International |
| spelling | doaj-art-95591020b3be4b90931dc744376dd30c2025-01-24T04:44:10ZengElsevierEnvironment International0160-41202025-01-01195109235A comprehensive characterization biotransformation of chlorinated paraffin by human and carp liver microsomes via liquid chromatography-high-resolution mass spectrometry and screening algorithmLiujun Chen0Caiming Tang1Zhiqiang Yu2Yanhong Zeng3Bixian Mai4Xiaojun Luo5State Key Laboratory of Organic Geochemistry and Guangdong Key Laboratory of Environmental Resources Utilization and Protection, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640, China; University of Chinese Academy of Sciences, Beijing 100049, ChinaLaboratory of Advanced Analytical Chemistry and Detection Technology, Research Center for Eco-Environmental Engineering, Dongguan University of Technology, Dongguan 523808, ChinaState Key Laboratory of Organic Geochemistry and Guangdong Key Laboratory of Environmental Resources Utilization and Protection, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640, ChinaState Key Laboratory of Organic Geochemistry and Guangdong Key Laboratory of Environmental Resources Utilization and Protection, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640, China; Guangdong-Hong Kong-MacaoChina Joint Laboratory for Environmental Pollution and Control, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640, ChinaState Key Laboratory of Organic Geochemistry and Guangdong Key Laboratory of Environmental Resources Utilization and Protection, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640, China; Guangdong-Hong Kong-MacaoChina Joint Laboratory for Environmental Pollution and Control, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640, ChinaState Key Laboratory of Organic Geochemistry and Guangdong Key Laboratory of Environmental Resources Utilization and Protection, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640, China; Guangdong-Hong Kong-MacaoChina Joint Laboratory for Environmental Pollution and Control, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640, China; Corresponding author at: State Key Laboratory of Organic Geochemistry and Guangdong Key Laboratory of Environmental Resources Utilization and Protection, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640, China.The chlorinated paraffin (CP) monomer 1,2,5,6,9,10-Hexachlorodecane (CP-4) was subjected to in vitro biotransformation using human and carp liver microsomes. Five types of CP-4 metabolites (OH–, keto-, enol-, aldehyde- and carboxy-CP-4) were identified in human liver microsomer while only mono-OH-CP-4 was found in the carp liver microsomes. Kinetic studies revealed that the formation of mono-, di-, tri-hydroxylated CP-4, keto-, enol-, and aldehyde-CP-4 in human liver microsomes was best described by substrate inhibition models, whereas the formation of carboxylated CP-4 metabolites best fit the Michaelis–Menten model. Notably, keto-CP-4, enol-CP-4 and aldehyde-CP-4 were the predominant metabolites. The estimated Vmax values for these metabolites were significantly higher in the human liver microsomes than in the carp liver microsomes. The intrinsic hepatic clearance (CLint) of CP-4 was higher in humans than in carp, indicating species-specific differences in its metabolism. This study also highlighted potential toxicity concerns, with computational predictions showing varying degrees of acute oral toxicity for CP-4 and its metabolites. These findings indicate significant species-specific differences in the biotransformation of CP-4, emphasizing the potential health and environmental risks associated with chlorinated paraffins and their metabolites, and underscore the need for further research to address these concerns.http://www.sciencedirect.com/science/article/pii/S0160412024008225Chlorinated ParaffinsBiotransformationLiver microsomesMetabolitesToxicity assessment |
| spellingShingle | Liujun Chen Caiming Tang Zhiqiang Yu Yanhong Zeng Bixian Mai Xiaojun Luo A comprehensive characterization biotransformation of chlorinated paraffin by human and carp liver microsomes via liquid chromatography-high-resolution mass spectrometry and screening algorithm Environment International Chlorinated Paraffins Biotransformation Liver microsomes Metabolites Toxicity assessment |
| title | A comprehensive characterization biotransformation of chlorinated paraffin by human and carp liver microsomes via liquid chromatography-high-resolution mass spectrometry and screening algorithm |
| title_full | A comprehensive characterization biotransformation of chlorinated paraffin by human and carp liver microsomes via liquid chromatography-high-resolution mass spectrometry and screening algorithm |
| title_fullStr | A comprehensive characterization biotransformation of chlorinated paraffin by human and carp liver microsomes via liquid chromatography-high-resolution mass spectrometry and screening algorithm |
| title_full_unstemmed | A comprehensive characterization biotransformation of chlorinated paraffin by human and carp liver microsomes via liquid chromatography-high-resolution mass spectrometry and screening algorithm |
| title_short | A comprehensive characterization biotransformation of chlorinated paraffin by human and carp liver microsomes via liquid chromatography-high-resolution mass spectrometry and screening algorithm |
| title_sort | comprehensive characterization biotransformation of chlorinated paraffin by human and carp liver microsomes via liquid chromatography high resolution mass spectrometry and screening algorithm |
| topic | Chlorinated Paraffins Biotransformation Liver microsomes Metabolites Toxicity assessment |
| url | http://www.sciencedirect.com/science/article/pii/S0160412024008225 |
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