S-oxygenation of eptam in hepatic microsomes from fresh- and saltwater striped bass (Morone saxatilis).
The in vitro liver microsomal oxidation of eptam (ethyl N,N-dipropylthiocarbamate) in the presence of freshwater and salt water adapted striped bass liver microsomes was investigated. In freshwater hepatic microsomes from striped bass, eptam is S-oxygenated in a process consistent with the involvement of monooxygenase activity. In contrast, both eptam S-oxide and eptam sulfone are formed in microsomes from salt water adapted striped bass microsomes in a process that is independent of monooxygenase activity and consistent with a role of cooxidation by hydroperoxy fatty acids. The mechanism of oxidation of eptam by hydroperoxy fatty acids may involve radical species. Both eptam S-oxide and eptam sulfone are efficient carbamylating agents toward thiol nucleophiles and react with substituted thiophenols to produce thiocarbamates while eptam itself is relatively stable to trans thiocarbamylation. Monooxygenase-catalyzed S-oxygenation of eptam in freshwater striped bass hepatic microsomes may represent a bioactivation route, which may explain the toxicity of thiocarbamate herbicides such as eptam toward freshwater fish.
Cashman
J R
JR
Department of Pharmaceutical Chemistry and Liver Center, School of Pharmacy, University of California, San Francisco 94143-0446.
Olsen
L D
LD
Young
G
G
Bern
H
H
D000818:Animals; D001492:Bass / Q000378:metabolism*; D002723:Chlorobenzoates / Q000737:chemistry; D005618:Fresh Water; D066298:In Vitro Techniques; D015227:Lipid Peroxidation; D009682:Magnetic Resonance Spectroscopy; D008862:Microsomes, Liver / Q000378:metabolism*; D012623:Seawater; D013739:Testosterone / Q000378:metabolism; D013859:Thiocarbamates / Q000138:chemical synthesis / Q000378:metabolism*
D002723:Chlorobenzoates; D013859:Thiocarbamates; D013739:Testosterone; C000433:3-chloroperbenzoic acid; C036251:EPTC