Bechtold W E, Henderson R F
Inhalation Toxicology Research Institute, Lovelace Biomedical and Environmental Research Institute, Albuquerque, New Mexico 87185.
J Toxicol Environ Health. 1993 Oct-Nov;40(2-3):377-86. doi: 10.1080/15287399309531803.
Three biomarkers for benzene exposure were developed. The first biomarker, muconic acid in urine, results from the ring opening of a benzene metabolite. A gas chromatography/mass spectroscopy (GC/MS) assay was developed to measure urinary muconic acid, and the analyte in urine samples from workers occupationally exposed to benzene was determined. Workers exposed to benzene concentrations as low as 4.4 ppm over an 8-h day showed higher urinary muconic acid concentrations than did any control individual (p < .005). The second biomarker, S-phenylcysteine (SPC) in hemoglobin (Hb), results from the addition of benzene oxide to a cysteine sulfhydryl group. A GC/MS assay was developed to measure SPC in the blood of F344/N rats and B6C3F1 mice exposed to benzene by inhalation. The cysteine moiety on rat Hb is at a more accessible site than on Hb of mice or humans, and rats showed considerably higher levels of SPC than did mice. As yet, we have been unable to detect SPC in the globin of humans occupationally exposed to benzene. The third biomarker is SPC in albumin. In humans occupationally exposed to average concentrations of 0, 4.4, 8.4, and 23.1 ppm benzene, 8 h/d, 5 d/wk, SPC increased in the exposed groups linearly, giving a statistically significant slope (p < .001) of 0.044 +/- 0.008 pmol/mg albumin/ppm. The assay for SPC is arduous and often imprecise; assuming these difficulties can be overcome, muconic acid in urine and SPC in albumin may be useful for accurately determining benzene exposure.
已开发出三种苯暴露生物标志物。第一种生物标志物是尿中的粘康酸，它是苯代谢产物开环的结果。已开发出一种气相色谱/质谱（GC/MS）分析法来测量尿中的粘康酸，并测定了职业性接触苯的工人尿液样本中的分析物。在8小时工作日内接触低至4.4 ppm苯浓度的工人，其尿中粘康酸浓度高于任何对照个体（p <.005）。第二种生物标志物是血红蛋白（Hb）中的S-苯基半胱氨酸（SPC），它是由苯氧化物加成到半胱氨酸巯基上产生的。已开发出一种GC/MS分析法来测量经吸入接触苯的F344/N大鼠和B6C3F1小鼠血液中的SPC。大鼠Hb上的半胱氨酸部分比小鼠或人类Hb上的更容易接近，并且大鼠的SPC水平明显高于小鼠。到目前为止，我们还无法在职业性接触苯的人类珠蛋白中检测到SPC。第三种生物标志物是白蛋白中的SPC。在职业性接触平均浓度为0、4.4、8.4和23.1 ppm苯、每天8小时、每周5天的人群中，暴露组的SPC呈线性增加，斜率为0.044±0.008 pmol/mg白蛋白/ppm，具有统计学显著性（p <.001）。SPC的测定过程艰巨且往往不精确；假设这些困难能够克服，尿中的粘康酸和白蛋白中的SPC可能有助于准确测定苯暴露情况。
