Styrene oxide in blood, hemoglobin adducts, and urinary metabolites in human volunteers exposed to (13)C(8)-styrene vapors.
Styrene is used in the manufacture of plastics and polymers and in the boat-building industry. The major metabolic route for styrene in rats, mice, and humans involves conversion to styrene-7,8-oxide (SO). The purpose of this study was to evaluate blood SO, SO-hemoglobin (SO-Hb) adducts, and urinary metabolites in styrene-exposed human volunteers and to compare these results with data previously obtained for rodents. Four healthy male volunteers were exposed for 2 h during light physical exercise to 50 ppm (13)C(8)-styrene vapor via a face mask. Levels and time profiles of styrene in exhaled air, blood, and urine (analyzed by GC) and urinary excretion patterns of mandelic acid and phenylglyoxylic acid in urine (analyzed by HPLC) were comparable to previously published volunteer studies. Maximum levels of SO in blood (measured by GC-MS) of 2.5-12.2 (average 6.7) nM were seen after 2 h, i.e., in the first sample collected after exposure had ended. The styrene blood level in humans was about 1.5 to 2 times higher than in rats and 4 times higher than in mice for equivalent styrene exposures. In contrast the SO levels in human blood was approximately fourfold lower than in mice. The level of hydroxyphenethylvaline (determined by GC-MS-MS) in pooled blood collected after exposure was estimated as 0.3 pmol/g globin corresponding to a SO-Hb adduct increment of about 0.003 pmol/g and ppmh. NMR analyses of urine showed that a major portion (> 95%) of the excreted (13)C-derived metabolites was derived from hydrolysis of SO, while only a small percentage of the excreted metabolites (< 5%) was derived from metabolism via phenylacetaldehyde. Signals consistent with metabolites derived from other pathways of styrene metabolism in rodents (such as glutathione conjugation with SO or ring epoxidation) were not detected.
Johanson
G
G
Toxicology and Risk Assessment, National Institute for Working Life, Stockholm, Sweden.
Ernstgård
L
L
Gullstrand
E
E
Löf
A
A
Osterman-Golkar
S
S
Williams
C C
CC
Sumner
S C
SC
D002247:Carbon Isotopes; D002851:Chromatography, High Pressure Liquid; D004852:Epoxy Compounds / Q000097:blood*; D006038:Glyoxylates / Q000652:urine; D006454:Hemoglobins / Q000378:metabolism*; D006626:Hippurates / Q000652:urine; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008333:Mandelic Acids / Q000652:urine; D020058:Styrene / Q000493:pharmacokinetics*; D014835:Volatilization
D002247:Carbon Isotopes; D004852:Epoxy Compounds; D006038:Glyoxylates; D006454:Hemoglobins; D006626:Hippurates; D008333:Mandelic Acids; C012482:phenylglyoxylic acid; D020058:Styrene; C013690:styrene oxide; C037938:mandelic acid; C030514:hippuric acid