Characterization of metabolites of benz(j)aceanthrylene in faeces, urine and bile from rat.
1. The excretion of benz[j]aceanthrylene (B[j]A) and the biotransformation products found in faeces, urine and bile of rat exposed to [3H]-labelled B[j]A have been studied. 2. About 95% of the administered radioactivity was excreted within 7 days, 79% via faeces and 16% via urine, and most of the radioactivity in urine and faeces was excreted within 2 days. 3. The B[j]A metabolites excreted between days 1 and 2, including those excreted in bile during the first 5.5 h in a separate experiment, were further characterized by HPLC, UV and electrospray/atmospheric pressure chemical ionization mass spectrometry. 4. In faeces, bile and urine, hydroxylated B[j]A metabolites predominated. The major metabolites in faeces were B[j]A-1,2-dihydrodiol-8-hydroxy and B[j]A-1,2-dihydrodiol-10-hydroxy. These metabolites were found as conjugated metabolites in the bile. The glucuronide conjugate of B[j]A-1,2-dihydrodiol-10-hydroxy was also a major metabolite in urine. Two sulphate conjugates of oxidized B[j]A were detected in bile, a sulphate conjugate of a B[j]A-dihydrodiol-phenol and B[j]A-1,2-dihydrodiol-10-sulphate. Trans-B[j]A-1,2-dihydrodiol was detected in urine, faeces and bile. 5. These findings support the hypothesis that epoxidation at the cyclopenta ring is an important biotransformation pathway for B[j]A in vivo. In addition to the characterized metabolites, a large fraction of polar compounds, possibly glutathione conjugates, was also excreted in urine and bile.
Hegstad
S
S
Department of Environmental Medicine, National Institute of Public Health, Oslo, Norway. solfrid.hegstad@folkehelsa.no
Lundanes
E
E
Holme
J A
JA
Alexander
J
J
D000818:Animals; D001646:Bile / Q000187:drug effects / Q000378:metabolism*; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005243:Feces; D008658:Inactivation, Metabolic; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D008748:Methylcholanthrene / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D009153:Mutagens / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D014316:Tritium; D014556:Urine; D014867:Water
D009153:Mutagens; D014867:Water; D014316:Tritium; D008748:Methylcholanthrene; C037411:benz(j)aceanthrylene