Boogaard P J, van Sittert N J
Shell Research BV, Shell Molecular Toxicology, Amsterdam, The Netherlands.
Occup Environ Med. 1995 Sep;52(9):611-20. doi: 10.1136/oem.52.9.611.
Comparison of the suitability of two minor urinary metabolites of benzene, trans,trans-muconic acid (tt-MA) and S-phenylmercapturic acid (S-PMA), as biomarkers for low levels of benzene exposure.
The sensitivity of analytical methods of measuring tt-MA and S-PMA were improved and applied to 434 urine samples collected from 188 workers in 12 studies in different petrochemical industries and from 52 control workers with no occupational exposure to benzene. In nine studies airborne benzene concentrations were assessed by personal air monitoring.
Strong correlations were found between tt-MA and S-PMA concentrations in samples from the end of the shift and between either of these variables and airborne benzene concentrations. It was calculated that exposure to 1 ppm (8 hour time weighted average (TWA)) benzene leads to an average concentration of 1.7 mg tt-MA and 47 micrograms S-PMA/g creatinine in samples from the end of the shift. It was estimated that, on average, 3.9% (range 1.9%-7.3%) of an inhaled dose of benzene was excreted as tt-MA with an apparent elimination half life of 5.0 (SD 2.3) hours and 0.11% (range 0.05%-0.26%) as S-PMA with a half life of 9.1 (SD 3.7) hours. The mean urinary S-PMA in 14 moderate smokers and 38 non-smokers was 3.61 and 1.99 micrograms/g creatinine, respectively and the mean urinary tt-MA was 0.058 and 0.037 mg/g creatinine, respectively. S-PMA proved to be more specific and more sensitive (P = 0.030, Fisher's exact test) than tt-MA. S-PMA, but not tt-MA, was always detectable in the urine of smokers who were not occupationally exposed. S-PMA was also detectable in 20 of the 38 non-smokers from the control group whereas tt-MA was detectable in only nine of these samples. The inferior specificity of tt-MA is due to relatively high background values (up to 0.71 mg/g creatinine in this study) that may be found in non-occupationally exposed people.
Although both tt-MA and S-PMA are sensitive biomarkers, only S-PMA allows reliable determination of benzene exposures down to 0.3 ppm (8 h TWA) due to its superior specificity. Because it has a longer elimination half life S-PMA is also a more reliable biomarker than tt-MA for benzene exposures during 12 hour shifts. For biological monitoring of exposure to benzene concentrations higher than 1 ppm (8 h TWA) tt-MA is also suitable and may even be preferred due to its greater ease of measurement.
比较苯的两种次要尿代谢物反式，反式-粘康酸（tt-MA）和S-苯巯基尿酸（S-PMA）作为低水平苯暴露生物标志物的适用性。
改进了测量tt-MA和S-PMA的分析方法的灵敏度，并将其应用于从12项不同石化行业研究中的188名工人以及52名无职业性苯暴露的对照工人收集的434份尿液样本。在9项研究中，通过个人空气监测评估空气中苯浓度。
在轮班结束时采集的样本中，tt-MA和S-PMA浓度之间以及这些变量中的任何一个与空气中苯浓度之间均发现强相关性。经计算，暴露于1 ppm（8小时时间加权平均值（TWA））苯会导致轮班结束时样本中tt-MA平均浓度为1.7 mg，S-PMA为47微克/克肌酐。据估计，平均而言，吸入剂量的苯中有3.9%（范围为1.9%-7.3%）以tt-MA形式排泄，表观消除半衰期为5.0（标准差2.3）小时，以S-PMA形式排泄的为0.11%（范围为0.05%-0.26%），半衰期为9.1（标准差3.7）小时。14名中度吸烟者和38名非吸烟者的尿S-PMA平均分别为3.61和1.99微克/克肌酐，尿tt-MA平均分别为0.058和0.037毫克/克肌酐。结果证明，S-PMA比tt-MA更具特异性和敏感性（P = 0.030，Fisher精确检验）。在无职业性苯暴露的吸烟者尿液中，总是能检测到S-PMA，但检测不到tt-MA。在对照组的38名非吸烟者中，有20人可检测到S-PMA，而这些样本中只有9人可检测到tt-MA。tt-MA特异性较差是由于在非职业性暴露人群中可能发现相对较高的背景值（本研究中高达0.71毫克/克肌酐）。
虽然tt-MA和S-PMA都是敏感的生物标志物，但由于其更高的特异性，只有S-PMA能够可靠地测定低至0.3 ppm（8小时TWA）的苯暴露。由于其消除半衰期更长，对于12小时轮班期间的苯暴露，S-PMA也是比tt-MA更可靠的生物标志物。对于高于1 ppm（8小时TWA）的苯浓度暴露的生物监测，tt-MA也适用，甚至可能因其测量更简便而更受青睐。
