In vitro toxicokinetics of ethylene and ethylene oxide in mice, rats, and humans:
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| Main Author: | |
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| Format: | Thesis Book |
| Language: | English |
| Published: |
2012
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| Subjects: | |
| Online Access: | Volltext https://nbn-resolving.org/urn:nbn:de:bvb:91-diss-20120803-1097598-1-5 Inhaltsverzeichnis |
| Physical Description: | II, 125 Bl. graph. Darst. |
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| 245 | 1 | 0 | |a In vitro toxicokinetics of ethylene and ethylene oxide in mice, rats, and humans |c Qiang Li |
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| 650 | 0 | 7 | |a Ethylen |0 (DE-588)4140264-9 |2 gnd |9 rswk-swf |
| 650 | 0 | 7 | |a Ethylenoxid |0 (DE-588)4153109-7 |2 gnd |9 rswk-swf |
| 655 | 7 | |0 (DE-588)4113937-9 |a Hochschulschrift |2 gnd-content | |
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Record in the Search Index
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| adam_text | IMAGE 1
TABLE OF CONTENTS
1 INTRODUCTION 1
1.1 OBJECTIVE 1
1.2 ETHYLENE AND ETHYLENE OXIDE 2
1.2.1 PHYSICOCHEMICAL PROPERTIES 2
1.2.2 PRODUCTION, USE, EXPOSURE, AND REGULATIONS 3
1.2.3 METABOLISM 5
1.2.4 GENOTOXICITY AND CARCINOGENICITY 7
1.2.5 TOXICOKINETICS 10
1.3 AIM OF THE WORK 14
2 MATERIALS AND METHODS 1 6
2.1 MATERIALS 16
2.1.1 CHEMICALS AND EQUIPMENT 16
2.1.2 ANIMALS AND LIVERS OR HEPATIC SUBCELLULAR FRACTIONS FROM HUMAN
DONORS 20
2.2 METHODS 23
2.2.1 GENOTYPING CYP2E1 IN WILD-TYPE AND CYP2E1 KNOCKOUT MICE 23
2.2.2 PREPARATION OF MICROSOMES, CYTOSOL, AND HOMOGENATES FROM DIVERSE
TISSUES 27
2.2.3 ANALYTICAL PROCEDURE 30
2.2.3.1 DETERMINATION OF ETHYLENE, ETHYLENE OXIDE, PROPYLENE OXIDE,
ACETALDEHYDE, AND STYRENE BY GAS CHROMATOGRAPHY WITH FLAME IONIZATION
DETECTION 30
2.2.3.2 DETERMINATION OF ETHYLENE OXIDE USING GAS CHROMATOGRAPHY WITH
MASSSELECTIVE DETECTION 35
2.2.3.3 DETERMINATION OF CYP2E1 ACTIVITY 37
2.2.3.4 QUANTIFICATION OF GLUTATHIONE 40
2.2.3.5 PROTEIN DETERMINATION 42
2.2.4 EXPOSURE EXPERIMENTS IN VITRO WITH ETHYLENE, ETHYLENE OXIDE,
PROPYLENE OXIDE, OR STYRENE 43
2.2.4.1 GENERAL PROCEDURE 43
2.2.4.2 MICROSOMAL INBUBATIONS 44
2.2.4.3 CYTOSOLIC INCUBATIONS 45
2.2.4.4 DETERMINATION OF DISTRIBUTION COEFFICIENTS AND DISTRIBUTION
FACTORS OF ETHYLENE AND ETHYLENE OXIDE 46
HTTP://D-NB.INFO/1028514441
IMAGE 2
2.2.4.5 INCUBATIONS OF TISSUE HOMOGENATES 49
2.2.5 TOXICOKINETIC ANALYSIS 50
2.2.6 STATISTICS 54
3 RESULTS 5 6
3.1 METHOD VALIDATION STUDIES 56
3.1.1 THE NADPH REGENERATING SYSTEM 56
3.1.2 DISTRIBUTION BETWEEN LIQUID PHASE AND AIR 57
3.1.3 MICROSOMAL AND CYTOSOLIC VIABILITY TESTS 59
3.1.4 GENOTYPING 64
3.2 INCUBATION STUDIES 65
3.2.1 GAS UPTAKE STUDIES WITH ETHYLENE IN MICROSOMAL INCUBATIONS 65
3.2.1.1 ELIMINATION OF ETHYLENE 65
3.2.1.2 QUANTITATIVE DESCRIPTION OF THE SUICIDE INACTIVATION OF CYP2E1
BY ETHYLENE; DEVELOPMENT OF A SUICIDE INHIBITION MODEL 67
3.2.1.3 FORMATION OF ETHYLENE OXIDE 71
3.2.1.4 ACETALDEHYDE, A POSSIBLE ETHYLENE METABOLITE? 82
3.2.2 GAS UPTAKE STUDIES WITH ETHYLENE OXIDE IN SUBCELLULAR FRACTIONS 83
3.2.2.1 ETHYLENE OXIDE IN MICROSOMAL INCUBATIONS 83
3.2.2.2 ETHYLENE OXIDE IN CYTOSOLIC INCUBATIONS 85
3.2.3 GAS UPTAKE STUDIES WITH ETHYLENE OXIDE IN TISSUE HOMOGENATES 89
4 DISCUSSION 9 4
4.1 CYTOCHROME P450 SUICIDE INACTIVATION 94
4.2 TOXICOKINETICS OF ETHYLENE 96
4.3 TOXICOKINETICS OF ETHYLENE OXIDE 98
4.4 ETHYLENE OXIDE BURDEN DURING EXPOSURE TO ETHYLENE 101
4.5 OUTLOOK 101
5 SUMMARY / ZUSAMMENFASSUNG 1 0 2
5.1 SUMMARY 102
5.2 ZUSAMMENFASSUNG 105
6 ABBREVIATIONS 1 0 9
7 REFERENCES 1 1 0
II
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| discipline | Chemie Medizin Ökotrophologie |
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| spelling | Li, Qiang Verfasser aut In vitro toxicokinetics of ethylene and ethylene oxide in mice, rats, and humans Qiang Li 2012 II, 125 Bl. graph. Darst. txt rdacontent n rdamedia nc rdacarrier München, Techn. Univ., Diss., 2012 Pharmakokinetik (DE-588)4115557-9 gnd rswk-swf Ethylen (DE-588)4140264-9 gnd rswk-swf Ethylenoxid (DE-588)4153109-7 gnd rswk-swf (DE-588)4113937-9 Hochschulschrift gnd-content Ethylen (DE-588)4140264-9 s Ethylenoxid (DE-588)4153109-7 s Pharmakokinetik (DE-588)4115557-9 s b DE-604 Erscheint auch als Online-Ausgabe urn:nbn:de:bvb:91-diss-20120803-1097598-1-5 http://mediatum.ub.tum.de/node?id=1097598 Verlag kostenfrei Volltext https://nbn-resolving.org/urn:nbn:de:bvb:91-diss-20120803-1097598-1-5 Resolving-System DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=025400033&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Li, Qiang In vitro toxicokinetics of ethylene and ethylene oxide in mice, rats, and humans Pharmakokinetik (DE-588)4115557-9 gnd Ethylen (DE-588)4140264-9 gnd Ethylenoxid (DE-588)4153109-7 gnd |
| subject_GND | (DE-588)4115557-9 (DE-588)4140264-9 (DE-588)4153109-7 (DE-588)4113937-9 |
| title | In vitro toxicokinetics of ethylene and ethylene oxide in mice, rats, and humans |
| title_auth | In vitro toxicokinetics of ethylene and ethylene oxide in mice, rats, and humans |
| title_exact_search | In vitro toxicokinetics of ethylene and ethylene oxide in mice, rats, and humans |
| title_full | In vitro toxicokinetics of ethylene and ethylene oxide in mice, rats, and humans Qiang Li |
| title_fullStr | In vitro toxicokinetics of ethylene and ethylene oxide in mice, rats, and humans Qiang Li |
| title_full_unstemmed | In vitro toxicokinetics of ethylene and ethylene oxide in mice, rats, and humans Qiang Li |
| title_short | In vitro toxicokinetics of ethylene and ethylene oxide in mice, rats, and humans |
| title_sort | in vitro toxicokinetics of ethylene and ethylene oxide in mice rats and humans |
| topic | Pharmakokinetik (DE-588)4115557-9 gnd Ethylen (DE-588)4140264-9 gnd Ethylenoxid (DE-588)4153109-7 gnd |
| topic_facet | Pharmakokinetik Ethylen Ethylenoxid Hochschulschrift |
| url | http://mediatum.ub.tum.de/node?id=1097598 https://nbn-resolving.org/urn:nbn:de:bvb:91-diss-20120803-1097598-1-5 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=025400033&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT liqiang invitrotoxicokineticsofethyleneandethyleneoxideinmiceratsandhumans |