Stereochemical metabolism of styrene in volunteersWenker, M.A.M.; Kezic, S.; Monster, A.C.; de Wolff, F.A.
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Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. Abstract Objectives: To study the stereochemistry of styrene metabolism in volunteers, and its interindividual variability. Methods: Twenty healthy male volunteers (aged 18±37 years) were exposed to 360 mg/m 3 styrene for 1 h while they performed 50 W physical exercise. Venous blood was drawn during and for up to 2 h after exposure. Urine was collected at time-intervals up to 24 h after exposure. The following parameters were determined: styrene, free and conjugated styrene glycol (SG) in blood, and conjugated SG, mandelic acid (MA) and phenylglyoxylic acid (PGA) in urine. Results: Average pulmonary retention of styrene was 62%. Excretion of the acidic metabolites MA and PGA accounted for 58% of the pulmonary uptake. The average maximum concentration (C max ) and area under the curve (AUC) of free (R)-SG in blood were 1.3 and 1.7 times higher than those of (S)-SG respectively; the half-life of (R)-SG was longer (82 vs 62 min, P < 0.005). C max and AUC of the conjugated SG enantiomers in blood did not di er, but again half-life for (R)-SG was longer (72 vs 64 min, P < 0.05). Cumulative excretion and renal clearance of conjugated (S)-SG in urine were three and four times higher, respectively, than that of (R)-SG. Cumulative excretion of (S)-MA was 1.6 times higher than (R)-MA. Interindividual di erences in the kinetic parameters of the metabolites were two-to threefold. Conclusions: The enantiomeric excess found was di erent for each metabolite under study, implying di erent enantioselectivity and/or enantiospeci®city of the enzymes and carrier-proteins involved in the biotransformation and excretion. The use of these metabolites as biological indicators for prediction of the enantiomeric excess of the toxic metabolite styrene-7,8-oxide (SO) is therefore not justi®ed. Interindividual di erences in the stereochemical metabolism of styrene are moderate.