Biotransformation of diethenylbenzenes. III: Identification of metabolites of 1,3-diethenylbenzene in rat.
1. Biotransformation of 1,3-diethenylbenzene (1) in rat gave four major metabolites, namely, 3-ethenylphenylglyoxylic acid (2), 3-ethenylmandelic acid (3), N-acetyl-S-[2-(3-ethenylphenyl)-2-hydroxyethyl]-L-cysteine (4) and N-acetyl-S-[1-(3-ethenylphenyl)-2-hydroxyethyl]-L-cysteine (5) were isolated from urine and identified by n.m.r. and mass spectrometry. 2. Four minor metabolites, 3-ethenylbenzoic acid (6), 3-ethenylphenylacetic acid (7), 3-ethenylbenzoylglycine (8) and 2-(3-ethenylphenyl)ethanol (9) were identified by g.l.c.-mass spectrometric analysis of urine extract derivatized in two different ways. 3. All identified metabolites are derived from 3-ethenylphenyloxirane (10), a reactive metabolic intermediate. No product of any metabolic transformation of second ethenyl group has been identified. However, several minor unidentified metabolites were detected by g.l.c.-mass spectrometry. 4. Total thioether excretion in 24 h urine after a single i.p. dose of 1 amounted to 28.3 +/- 3.5 dose (mean +/- SD). No significant differences in the thioether fraction were observed in the dose range 100-300 mg/kg. 5. Thioether metabolites consisted mainly of mercapturic acids 4 and 5. The ratio of metabolites 5 to 4 was 62:38. Each mercapturic acid consisted of two diastereomers. Their ratio, as determined by quantitative 13C-n.m.r. measurement was 95:5 and 79:21 for mercapturic acids 4 and 5, respectively.
Linhart
I
I
Centre of Industrial Hygiene and Occupational Diseases, Prague, Czechoslovakia.
Mitera
J
J
Vosmanská
M
M
Smejkal
J
J
Pech
P
P
D000818:Animals; D001711:Biotransformation; D005260:Female; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D051381:Rats; D011919:Rats, Inbred Strains; D013343:Styrenes / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D015262:Xenobiotics / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity
D013343:Styrenes; D015262:Xenobiotics; C076011:1,3-diethenylbenzene