Scherer G, Renner T, Meger M
Analytisch-biologisches Forschungslabor ABF, Munich, Germany.
J Chromatogr B Biomed Sci Appl. 1998 Oct 9;717(1-2):179-99. doi: 10.1016/s0378-4347(98)00065-6.
Benzene is an important industrial chemical and, due to its occurrence in mineral oil and its formation in many combustion processes, a widespread environmental pollutant. Since benzene is hematoxic and has been classified as a human carcinogen, monitoring and control of benzene exposure is of importance. Although trans,trans-muconic acid (ttMA) was identified as a urinary metabolite of benzene at the beginning of this century, only recently has its application as a biomarker for occupational and environmental benzene exposure been investigated. The range of metabolic conversion of benzene to ttMA is about 2-25% and dependent on the benzene exposure level, simultaneous exposure to toluene, and probably also to genetic factors. For the quantitation of ttMA in urine, HPLC methods using UV and diode array detection as well as GC methods combined with MS or FID detection have been described. Sample pretreatment for both HPLC and GC analysis comprises centrifugation and enrichment by solid-phase extraction on anion-exchange sorbents. Described derivatization procedures prior to GC analysis include reaction with N,O-bis(trimethysilyl)acetamide, N,O-bis(trimethylsilyl)trifluoroacetamide, pentafluorobenzyl bromide and borontrifluoride-methanol. Reported limits of detection for HPLC methods range from 0.1 to 0.003 mg l(-1), whereas those reported for GC methods are 0.03-0.01 mg l(-1). Due to its higher specificity, GC methods appear to be more suitable for determination of low urinary ttMA levels caused by environmental exposure to benzene. In studies with occupational exposure to benzene (>0.1 ppm), good correlations between urinary ttMA excretion and benzene levels in breathing air are observed. From the reported regressions for these variables, mean excretion rates of ttMA of 1.9 mg g(-1) creatinine or 2.5 mg l(-1) at an exposure dose of 1 ppm over 8 h can be calculated. The smoking-related increase in urinary ttMA excretion reported in twelve studies ranged from 0.022 to 0.2 mg g(-1) creatinine. Only a few studies have investigated the effect of exposure to environmental levels of benzene (<0.01 ppm) on urinary ttMA excretion. A trend for slightly increased ttMA levels in subjects living in areas with high automobile traffic density was observed, whereas exposure to environmental tobacco smoke did not significantly increase the urinary ttMA excretion. It is concluded that urinary ttMA is a suitable biomarker for benzene exposure at occupational levels as low as 0.1 ppm. Biomonitoring of exposure to environmental benzene levels (<0.01 ppm) using urinary ttMA appears to be possible only if the ingestion of dietary sorbic acid, another precursor to urinary ttMA, is taken into account.
苯是一种重要的工业化学品，由于其存在于矿物油中且在许多燃烧过程中形成，是一种广泛存在的环境污染物。由于苯具有血液毒性并已被列为人类致癌物，因此监测和控制苯暴露至关重要。尽管反式，反式粘康酸（ttMA）在本世纪初被确定为苯的尿代谢产物，但直到最近才对其作为职业和环境苯暴露生物标志物的应用进行了研究。苯向ttMA的代谢转化率约为2 - 25%，取决于苯暴露水平、同时接触甲苯的情况，可能还与遗传因素有关。对于尿液中ttMA的定量分析，已经描述了使用紫外和二极管阵列检测的高效液相色谱法以及与质谱或火焰离子化检测相结合的气相色谱法。高效液相色谱和气相色谱分析的样品预处理包括离心和通过阴离子交换吸附剂进行固相萃取富集。气相色谱分析之前描述的衍生化程序包括与N，O - 双（三甲基硅基）乙酰胺、N，O - 双（三甲基硅基）三氟乙酰胺、五氟苄基溴和三氟化硼 - 甲醇反应。报道的高效液相色谱法的检测限范围为0.1至0.003 mg l(-1)，而气相色谱法报道的检测限为0.03 - 0.01 mg l(-1)。由于其更高的特异性，气相色谱法似乎更适合测定环境暴露于苯引起的低水平尿ttMA。在职业性接触苯（>0.1 ppm）的研究中，观察到尿ttMA排泄与呼吸空气中苯水平之间有良好的相关性。根据这些变量报道的回归方程，可以计算出在8小时内暴露剂量为1 ppm时ttMA的平均排泄率为1.9 mg g(-1)肌酐或2.5 mg l(-1)。十二项研究报道的与吸烟相关的尿ttMA排泄增加范围为0.022至0.2 mg g(-1)肌酐。只有少数研究调查了环境水平的苯（<0.01 ppm）暴露对尿ttMA排泄的影响。观察到生活在汽车交通密度高的地区的受试者中ttMA水平有轻微升高的趋势，而暴露于环境烟草烟雾并未显著增加尿ttMA排泄。得出的结论是，尿ttMA是职业水平低至0.1 ppm苯暴露的合适生物标志物。仅当考虑膳食山梨酸（尿ttMA的另一种前体）的摄入量时，使用尿ttMA对环境苯水平（<0.01 ppm）的暴露进行生物监测似乎才有可能。
