Stereochemical metabolism of styrene in volunteers

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• 作者：Mira A. M. Wenker ; Sanja Ke?i? ; Aart C. Monster and Frederik A. de Wolff
• 关键词：Key words Styrene ; Stereoisomerism ; Styrene glycol ; Mandelic acid ; metabolism
• 刊名：International Archives of Occupational and Environmental Health
• 出版年：2001
• 出版时间：July 2001
• 年：2001
• 卷：74
• 期：5
• 页码：359-365
• 全文大小：126 KB
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Occupational and Industrial Medicine
  Environmental Medicine/Environmental Psychology
  Rehabilitation
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-1246

文摘

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/m3 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 differ, 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 differences in the kinetic parameters of the metabolites were two- to threefold. Conclusions: The enantiomeric excess found was different for each metabolite under study, implying different enantioselectivity and/or enantiospecificity 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 justified. Interindividual differences in the stereochemical metabolism of styrene are moderate.