Fustinoni S, Colosio C, Colombi A, Lastrucci L, Yeowell-O'Connell K, Rappaport S M
Istituti Clinici di Perfezionamento, Milan, Italy.
Int Arch Occup Environ Health. 1998 Feb;71(1):35-41. doi: 10.1007/s004200050247.
The purpose of this work was to compare levels of styrene-7,8-oxide (SO) adducts of albumin (Alb) and hemoglobin (Hb) with those of two urinary metabolites of styrene, mandelic acid (MA) and phenylglyoxylic acid (PGA), among workers exposed to styrene in the reinforced-plastics industry and in unexposed subjects. We also wished to determine whether cigarette smoking influenced adduct levels among these subjects.
A group of 22 male workers was selected on basis of an expectedly high level of exposure to styrene, and a group of 15 controls was selected from hospital blood donors and hospital staff. In the exposed group, MA and PGA were quantified by high-performance liquid chromatography (HPLC) analysis of urine samples collected prior to the work shift. The SO adducts were cleaved from cysteine residues by reaction with Raney nickel to give 1-phenylethanol (1-PE) and 2-phenylethanol (2-PE), which, after derivatization, were measured using gas chromatography-mass spectrometry (GC-MS) in the negative-chemical-ionization (NCI) mode.
The estimated mean levels of MA and MA + PGA were 74 and 159 mg/g creatinine, respectively. Using the levels of urinary metabolites, an average styrene concentration of about 100 mg/m3 in the workplace air was estimated. The mean levels of 2-PE and 1-PE adducts in exposed workers were 2.84 and 0.60 nmol/g Alb and 5.44 and 0.43 nmol/g Hb, respectively. When subjects were stratified by level of urinary metabolites [zero (controls), low-level exposure (MA + PGA < or = 159 mg/g creatinine), and high-level exposure (MA + PGA > 159 mg/g creatinine)] and smoking status (smokers versus nonsmokers), a difference in Alb adduct levels was found among the groups (2-PE P = 0.002, I-PE P = 0.052). The difference in 2-PE-Alb levels was related to exposure category, to smoking status, and to their interaction. Correlations at or near a 0.05 level of significance were observed among the workers (n = 22) between individual levels of SO-protein adducts and MA + PGA (2-PE Alb, r = 0.54, 2-PE Hb, r = 0.40).
Our data suggest that only exposure to relatively high levels of styrene allows a clear relationship to be detected between styrene exposure and SO adducts, due in part to the effects of cigarette consumption and to the high background levels of these adducts observed in unexposed subjects.
本研究旨在比较强化塑料行业中接触苯乙烯的工人与未接触者的白蛋白（Alb）和血红蛋白（Hb）的苯乙烯-7,8-氧化物（SO）加合物水平，以及苯乙烯的两种尿代谢产物扁桃酸（MA）和苯乙醛酸（PGA）的水平。我们还希望确定吸烟是否会影响这些受试者的加合物水平。
基于预期的高苯乙烯暴露水平，选取了一组22名男性工人，并从医院献血者和医院工作人员中选取了一组15名对照者。在暴露组中，通过高效液相色谱（HPLC）分析轮班前采集的尿液样本，对MA和PGA进行定量。通过与雷尼镍反应，从半胱氨酸残基上裂解SO加合物，生成1-苯乙醇（1-PE）和2-苯乙醇（2-PE），衍生化后，使用气相色谱-质谱联用仪（GC-MS）在负化学电离（NCI）模式下进行测定。
MA和MA + PGA的估计平均水平分别为74和159 mg/g肌酐。根据尿代谢产物水平，估计工作场所空气中苯乙烯的平均浓度约为100 mg/m³。暴露工人中2-PE和1-PE加合物的平均水平分别为2.84和0.60 nmol/g Alb以及5.44和0.43 nmol/g Hb。当根据尿代谢产物水平[零（对照组）、低水平暴露（MA + PGA≤159 mg/g肌酐）和高水平暴露（MA + PGA>159 mg/g肌酐）]和吸烟状况（吸烟者与非吸烟者）对受试者进行分层时，发现各亚组之间Alb加合物水平存在差异（2-PE P = 0.002，1-PE P = 0.052）。2-PE-Alb水平的差异与暴露类别、吸烟状况及其相互作用有关。在22名工人中，观察到SO-蛋白质加合物个体水平与MA + PGA之间存在显著相关性（P≤0.05）（2-PE Alb，r = 0.54；2-PE Hb，r = 0.40）。
我们的数据表明，只有接触相对高水平的苯乙烯，才能检测到苯乙烯暴露与SO加合物之间的明确关系，部分原因是吸烟的影响以及在未接触者中观察到的这些加合物的高背景水平。
