Kim Sungkyoon, Vermeulen Roel, Waidyanatha Suramya, Johnson Brent A, Lan Qing, Rothman Nathaniel, Smith Martyn T, Zhang Luoping, Li Guilan, Shen Min, Yin Songnian, Rappaport Stephen M
School of Public Health, University of North Carolina, Chapel Hill, NC 27599, and National Cancer Institute (NCI), National Institutes of Health (NIH), Department of Health and Human Services (DHHS), Bethesda, MD 20892, USA.
Carcinogenesis. 2006 Apr;27(4):772-81. doi: 10.1093/carcin/bgi297. Epub 2005 Dec 8.
Although the toxicity of benzene has been linked to its metabolism, the dose-related production of metabolites is not well understood in humans, particularly at low levels of exposure. We investigated unmetabolized benzene in urine (UBz) and all major urinary metabolites [phenol (PH), E,E-muconic acid (MA), hydroquinone (HQ) and catechol (CA)] as well as the minor metabolite, S-phenylmercapturic acid (SPMA), in 250 benzene-exposed workers and 139 control workers in Tianjin, China. Median levels of benzene exposure were approximately 1.2 p.p.m. for exposed workers (interquartile range: 0.53-3.34 p.p.m.) and 0.004 p.p.m. for control workers (interquartile range: 0.002-0.007 p.p.m.). (Exposures of control workers to benzene were predicted from levels of benzene in their urine.) Metabolite production was investigated among groups of 30 workers aggregated by their benzene exposures. We found that the urine concentration of each metabolite was consistently elevated when the group's median benzene exposure was at or above the following air concentrations: 0.2 p.p.m. for MA and SPMA, 0.5 p.p.m. for PH and HQ, and 2 p.p.m. for CA. Dose-related production of the four major metabolites and total metabolites (micromol/l/p.p.m. benzene) declined between 2.5 and 26-fold as group median benzene exposures increased between 0.027 and 15.4 p.p.m. Reductions in metabolite production were most pronounced for CA and PH<1 p.p.m., indicating that metabolism favored production of the toxic metabolites, HQ and MA, at low exposures.
尽管苯的毒性与其代谢有关，但在人类中，尤其是在低暴露水平下，代谢物的剂量相关产生情况尚未得到很好的理解。我们在中国天津的250名苯暴露工人和139名对照工人中，对尿液中的未代谢苯（UBz）、所有主要尿代谢物[苯酚（PH）、E,E-粘康酸（MA）、对苯二酚（HQ）和儿茶酚（CA）]以及次要代谢物S-苯基巯基尿酸（SPMA）进行了调查。暴露工人的苯暴露中位数水平约为1.2 ppm（四分位间距：0.53 - 3.34 ppm），对照工人为0.004 ppm（四分位间距：0.002 - 0.007 ppm）。（根据对照工人尿液中的苯水平预测其苯暴露情况。）按苯暴露水平将30名工人分为一组，对各组的代谢物产生情况进行了调查。我们发现，当组内苯暴露中位数达到或高于以下空气浓度时，每种代谢物的尿液浓度持续升高：MA和SPMA为0.2 ppm，PH和HQ为0.5 ppm，CA为2 ppm。随着组内苯暴露中位数在0.027至15.4 ppm之间增加，四种主要代谢物和总代谢物的剂量相关产生量（微摩尔/升/ppm苯）下降了2.5至26倍。当苯暴露水平低于1 ppm时，CA和PH的代谢物产生量减少最为明显，这表明在低暴露水平下，代谢倾向于产生毒性代谢物HQ和MA。
