Toggle Main Menu Toggle Search

Open Access padlockePrints

In vitro metabolism of chloroprene: Species differences, epoxide stereochemistry and a de-chlorination pathway

Lookup NU author(s): Professor Bernard Golding, Dr Tony Munter, Professor William Watson

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


Abstract

Chloroprene (1) was metabolized by liver microsomes from Sprague-Dawley rats, Fischer 344 rats, B6C3F1 mice, and humans to the monoepoxides, (1-chloro-ethenyl)oxirane (5a/5b), and 2-chloro-2-ethenyloxirane (4a/4b). The formation of 4a/4b was inferred from the identification of their degradation products. With male Sprague-Dawley and Fischer 344 rat liver microsomes, there was a ca. 3:2 preference for the formation of (R)-(1-chloroethenyl)oxirane (5a) compared to the (S)-enantiomer (5b). A smaller but distinct enantioselectivity in the formation of (S)-(1-chloro-ethenyl)oxirane occurred with liver microsomes from male mouse (R:S, 0.90:1) or male human (R:S, 0.86:1). 2-Chloro-2-ethenyloxirane was very unstable in the presence of the microsomal mixture and was rapidly converted to 1-hydroxybut-3-en-2-one (11) and 1-chlorobut-3-en-2-one (12). An additional rearrangement pathway of 2-chloro-2-ethenyloxirane gave rise to 2-chlorobut-3-en-1-al (14) and 2-chlorobut-2-en-1-al (15). Further reductive metabolism of these metabolites occurred to form 1-hydroxybutan-2-one (17) and 1-chlorobutan-2-one (18). In the absence of an epoxide hydrolase inhibitor, the microsomal incubations converted (1-chloroethenyl)oxirane to 3-chlorobut-3-ene-1,2-diol (21a/21b). When microsomal incubations were supplemented with glutathione, 1-hydroxybut-3-en-2-one was not detected because of its rapid conjugation with this thiol scavenger.


Publication metadata

Author(s): Cottrell L, Golding BT, Munter T, Watson WP

Publication type: Article

Publication status: Published

Journal: Chemical Research in Toxicology

Year: 2001

Volume: 14

Issue: 11

Pages: 1552-1562

ISSN (print): 0893-228X

ISSN (electronic): 1520-5010

Publisher: American Chemical Society

URL: http://dx.doi.org/10.1021/tx0155404

DOI: 10.1021/tx0155404


Altmetrics

Altmetrics provided by Altmetric


Actions

Find at Newcastle University icon    Link to this publication


Share