US EPA

625214 

Journal Article 

Detoxication pathways involving glutathione and epoxide hydrolase in the in vitro metabolism of chloroprene 

Munter, T; Cottrell, L; Golding, BT; Watson, WP 

2003 

Yes 

Chemical Research in Toxicology
ISSN: 0893-228X
EISSN: 1520-5010 

Chem Res Toxicol. 

16 

10 

1287-1297 

English 

14565770 

10.1021/tx034107m 

WOS:000186103200012 

https://search.proquest.com/docview/19199729?accountid=171501
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Chloroprene (2-chloro-1,3-butadiene, 1) is an important industrial chemical, which is carcinogenic in experimental animals and possibly in humans. It is metabolized to the monoepoxides, 2-chloro-2-ethenyloxirane (2a,b) and (1-chloroethenyl)oxirane (3a,b), together with electrophilic chlorinated aldehydes and ketones. This study has investigated the detoxication of these chloroprene metabolites in vitro by glutathione (GSH) and epoxide hydrolase (EH) in liver microsomes from Sprague-Dawley rats, B6C3F1 mice, and humans. In incubations of chloroprene with liver microsomes containing GSH, several GSH conjugates were identified. These were 1-hydroxy-4-(S-glutathionyl)butan-2-one (13), 1,4-bis-(S-glutathionyl) butan-2-one (15), and (Z)-2-(S-glutathionyl)but-2-en-1-al (16). A fourth GSH conjugate was
identified as either 2-chloro-3-hydroxy-4-(S-glutathionyl)butene (12a,b) or 1-chloro-4-(Sglutathionyl)- butan-2-one (14), which were indistinguishable by LC/MS. Structural assignments of metabolites were based on chromatographic and spectroscopic comparisons with synthetic
standards. There were significant differences between species in the amounts of 3a,b formed in microsomal incubations, the order being mouse > rat > human. Hydrolysis by microsomal EHs showed a distinct selectivity for S-(1-chloroethenyl)oxirane (3b) resulting in an accumulation of the R-enantiomer; the ratio of the amounts between species was 20:4:1 for mouse:rat: human, respectively. 

chloroprene; in vitro; metabolism; Toxicology Abstracts; Detoxification; Epoxide hydrolase; Glutathione; X 24153:Metabolism