Comparative metabolism and disposition of ethoxyquin in rat and mouse. II. Metabolism.
1. The major pathways of ethoxyquin (EQ) metabolism in both the rat and mouse are O-deethylation and conjugation to endogenous substrates. 2. The two major EQ-derived metabolites excreted in rat urine were in the form of sulphate conjugates, 1,2-dihydro-6-hydroxy-2,2,4-trimethylquinoline sulphate, and 1,2,3,4-tetrahydro-3,6-dihydroxy-4-methylene-2,2-dimethylquinoline sulphate. The latter apparently arises from an intramolecular rearrangement of the 3,4-epoxide of ethoxyquin. 3. Mouse urine contained one major glucuronide, 1,2-dihydro-6-hydroxy-2,2,4-trimethylquinoline glucuronide as well as one major sulphate conjugate, 1,2-dihydro-6-hydroxy-2,2,4-trimethylquinoline sulphate. 4. EQ-derived radioactivity was excreted in rat bile, mainly as GSH conjugates, with little unchanged EQ present. Two of the biliary metabolites are glutathione conjugates of ethoxyquin 3,4-epoxide; the third appears to be a conjugate of either ethoxyquin 7,8-epoxide or 2,2,4-trimethylquinol-6-one.
Burka
L T
LT
Chemistry Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Sanders
J M
JM
Matthews
H B
HB
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001646:Bile / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005015:Ethoxyquin / Q000008:administration & dosage / Q000378:metabolism* / Q000652:urine; D005243:Feces / Q000737:chemistry; D005965:Glucuronates / Q000652:urine; D005966:Glucuronidase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D051381:Rats; D011916:Rats, Inbred F344; D013431:Sulfates / Q000652:urine
D000975:Antioxidants; D005965:Glucuronates; D013431:Sulfates; D005015:Ethoxyquin; D005966:Glucuronidase; D005978:Glutathione