Styrene oxide in blood, hemoglobin adducts, and urinary metabolites in human volunteers exposed to C-13(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, an d 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 resul ts with data previously obtained for rodents. Four healthy male volunteers were exposed for 2 h during light physical exercise to 50 ppm C-13(8)-styre ne vapor via a face mask. Levels and time profiles of styrene in exhaled ai r, blood, and urine (analyzed by GC) and urinary excretion patterns of mand elic acid and phenylglyoxylic acid in urine (analyzed by HPLC) were compara ble to previously published volunteer studies. Maximum levels of SO in bloo d (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 bloo d 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 le vels in human blood was approximately fourfold lower than in mice. The leve l of hydroxyphenethylvaline (determined by GC-MS-MS) in pooled blood collec ted 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 C-13-derived metabolite s was derived from hydrolysis of SO, while only a small percentage of the e xcreted metabolites (<5%) was derived from metabolism via phenylacetaldehyd e. Signals consistent with metabolites derived from other pathways of styre ne metabolism in rodents (such as glutathione conjugation with SO or ring e poxidation) were not detected. (C) 2000 Academic Press.