尿酚在苯的生物学监测中实用价值的评估

本文以苯的新型生物学指标粘康酸为对照，评估了尿酚在不同苯接触浓度下的生物学监测效果。选择了三个接触不同苯浓度范围工厂内的３２６名工人为研究对象。结果三个工厂受检者接触苯浓度的范围与几何均值分别为０．２９～８．６７ｍｇ／ｍ３、３．１２～５６．８７ｍｇ／ｍ３、１７．２５～３６８．５２ｍｇ／ｍ３与２．５３ｍｇ／ｍ３、２１．０１ｍｇ／ｍ３、９４．０７ｍｇ／ｍ３。而尿酚与空气苯的相关系数分别为０．６１０７、０．７２４５、０．８０１４。相应粘康酸与空气苯的相关系数分别为０．８２１３、０．９１０７、０．８６５１。此结果说明尿酚在接触苯浓度较低时，难以反映内吸收情况。而粘康酸则能敏感地反映接触较低苯浓度环境时个体的内吸收剂量。     

尿粘康酸在苯的生物监测中的应用价值

为研究苯暴露的生物标志物，应用改进的高压液相色谱法检测了１２８名苯接触工人及４０名对照人群的尿粘康酸含量，同时测定了其尿酚含量。结果表明，当空气苯浓度为４１．４９ｍｇ／ｍ３时，接触工人的尿粘康酸含量为（５．４７±７．９４）ｍｇ／ｇＣｒ，尿酚为（３９．０９±４２．５９）ｍｇ／ｇＣｒ。对照人群的尿粘康酸含量为（０．１３±０．０９）ｍｇ／ｇＣｒ，尿酚为（１６．０１±１１．３３）ｍｇ／ｇＣｒ（均为肌酐校正值，ｘＧ±ｓ）。苯接触工人的尿粘康酸含量与所接触的空气苯浓度及尿酚含量呈良好的相关，相关系数分别为０．９１８７，０．８２０４。尿粘康酸在人群中本底值低，反映苯的内吸收情况比尿酚更特异、敏感，更适于低浓度苯暴露的生物监测。     

尿酚在苯的生物学监测实用价值的评估

本文以苯的新型生物学指标粘康酸的对照，评估了尿酚在不同苯接触浓度下的生物学监测效果，选择了三个接触的不同苯浓度范围工厂内的３２６名工人为研究对象，结果三个工厂受检者接触苯浓度的范围与几何均值分别为０．２９～８．６７ｍｇ／ｍ＾３，３．１２～５６．８７ｍｇ／ｍ＾３，１７．２５～３６８．５２ｍｇ／ｍ＾３与２．５３ｍｇ／ｍ＾３，２１．０１ｍｇ／ｍ＾３，９４．０７ｍｇ／ｍ＾３而尿酚与空气苯的相关系数分别为０     

尿中粘康酸HPLC方法检测在苯生物监测中的应用研究

尿粘康酸是苯代谢产物中的一个极小分支，由于其在体内极低的本底值而受到重视。本研究采用强阴离子交换树脂预处理尿样，用ＨＰＬＣ—ＵＶ检测苯作业工人班前班末尿粘康酸浓度，并与尿酚及个体苯加权平均浓度进行相关分析。研究发现，苯作业工人尿粘康酸与尿酚、苯加权平均浓度三者之间良好相关，尿粘康酸比尿酚具备更好的敏感性与特异性，并能在个体苯加权平均浓度约３．８ｍｇ／ｍ￣３水平区分个体苯接触，尿粘康酸在苯生物监测中前景广阔。     

尿粘康酸作为苯内接触剂量的应用

为将尿粘康酸（ＴＴＭＡ）应用于苯接触人群的检测，应用高效液相色谱－紫外检测器系统检测苯接触人群尿ＴＴＭＡ。结果显示，尿ＴＴＭＡ在苯接触人群中有显著增加，随着空气苯浓度的增加，尿ＴＴＭＡ增加显著，显示出良好的相关关系（ｒ＝０．９４０，Ｐ＜０．０５）。当苯接触浓度为均值２．４６２ｍｇ／ｍ３时，接触人群尿ＴＴＭＡ与对照组相比，其差异具有统计学意义。提示，尿ＴＴＭＡ可作为苯接触特异、灵敏的生物检测指标，尤其对于低苯接触。尿ＴＴＭＡ在男女苯接触人群中差异无显著性。甲苯可抑制尿ＴＴＭＡ的形成。应用协方差分析可粗略校正甲苯的混杂作用。     

苯接触的生物监测指标初步评估

目的：探索可客观反映职业性苯危害的灵敏指标。方法：测定苯作业车间空气苯浓度和３３名苯作业工人及４名非苯作业工人志愿者苯接触后呼出苯浓度、血苯含量及尿酚排出量，并进行相关性分析。结果：空气苯浓度（４．５～３４８ｍｇ／ｍ３）与血苯含量呈明显正相关（Ｐ＜０．０５）；血苯含量与尿酚排出量呈非常显著正相关（Ｐ＜０．０１）。结论：在低浓度苯接触时，血苯是一个与毒性相关联的特异性敏感苯吸收指标；尿酚排出量可用作高浓度苯接触工人的生物监测指标。     

人尿中酚,粘糠酸,苯巯基尿酸的生物监测

为了探索接触低浓度苯的生物监测指标，在建立了灵敏、特异的尿中反，反－粘糠酸（ｔ，ｔ－ＭＡ）的高效液相色谱（ＨＰＬＣ）、苯巯基尿酸（Ｓ－ＰＭＡ）的色谱／质谱／质谱（ＬＣ／ＭＳ／ＭＳ）测定方法的基础上，对４９位接触低浓度苯的工人及２０位非职业接触者进行了生物监测。结果表明：在苯接触浓度低于３．２ｍｇ／ｍ３（１ｐｐｍ）的情况下，作业工人的尿ｔ，ｔ－ＭＡ和Ｓ－ＰＭＡ浓度与空气中苯的ＴＷＡ浓度显著相关；尿酚与空气中苯的ＴＷＡ浓度之间的相关性很差。吸烟能增加尿ｔ，ｔ－ＭＡ和Ｓ－ＰＭＡ的浓度。     

高压氧对苯中毒预防作用的实验研究

将大鼠置实验用高压氧舱内,在２个大气压下吸９９５％纯氧,每天２ｈ,连续５ｄ,最后一次吸氧后,即给予低、高两种浓度（４５０ｍｇ／ｍ３、３００ｍｇ／ｍ３）的苯染毒,测定血中超氧化物歧化酶（ＳＯＤ）,丙二醛（ＭＤＡ）及谷丙转氨酶（ＡＬＴ）;尿中尿酚、反,反—粘康酸。结果：吸氧高浓度苯（４５０ｍｇ／ｍ３）染毒组较不吸氧高浓度苯染毒组ＡＬＴ、反、反—粘康酸显著下降（Ｐ＜００５）;ＭＤＡ显著上升（Ｐ＜００５）,而ＳＯＤ、尿酚则变化不明显。低浓度苯染毒大鼠吸氧组除尿酚,反、反—粘康酸较不吸氧组升高较为明显外（无统计学意义）,其余均无明显差异。结论：高压氧只能降低高浓度苯中毒的危险性,对低浓度苯染毒作用不明显。     

职业性锰接触与尿锰、发锰关系的探讨

对锰矿及其加工厂接触锰工人５３６人、同厂矿其他工种工人５２人和行政对照组５３人进行体检及发锰、尿锰测定，同时进行环境检测。作业环境空气中ＭｎＯ２平均浓度波动范围０．１～１．８５ｍｇ／ｍ３；粉尘平均浓度在０．２２～８．０７ｍｇ／ｍ３。尿锰及发锰均值接触组、其他工种、对照组分别为０．２７９４μｍｏｌ／Ｌ及０．３２７６μｍｏｌ／ｇ，０．１６４９μｍｏｌ／Ｌ及０．２５１９μｍｏｌ／ｇ，０．１１８７μｍｏｌ／Ｌ及０．０７６６μｍｏｌ／ｇ。尿锰、发锰与空气锰及粉尘浓度间、与症状体征间未发现相关关系，认为尿锰、发锰目前只能作为锰接触指标，还不能作为锰接触工人的生物监测指标或早期锰中毒的诊断指标。     

空气苯浓度与呼出苯及尿酚的关系研究

目的对苯接触水平和接触者可能受到的有害影响进行卫生学评价。方法对１０名苯接触者和６名志愿苯接触者进行研究,用苯呼出气作为生物学监测指标。结果班前呼出苯大多为未检出,班中及班后呼出苯与空气苯时间加权平均浓度均有密切相关;班前尿酚与空气苯时间加权平均浓度无相关,班后尿酚及次晨尿酚均与空气苯ＴＷＡ浓度密切相关;班中、班后呼出苯均与班后尿酚及次晨尿酚密切相关,且以班中呼出苯与班后尿酚的相关性最高（ｒ＝０．９３５３）。呼出苯的快速排出相为脱离接触１０分钟（占班后呼出苯８２．２５％）,其排出稳定相在脱离接触后９０分钟左右。接触空气苯浓度ＴＷＡ７．９～２１７．８ｍｇ／ｍ３时,无论是呼出苯或尿酚在接触后２４小时与空气苯均无相关。结论在呼出苯的快速排出相采集终末呼出气可反映工人当时的接触浓度,采集排出稳定相终末呼出气,其浓度较稳定可反映接触者吸收入血液的浓度,并以此来估测环境浓度与接触水平。呼出苯的呼吸排出规律以及采样方便、无损伤,检出灵敏,呼出苯作为接触水平监测指标较其他指标优越。     

Evaluation of occupational exposure to benzene by urinalysis

Urinary phenol determinations have traditionally been used to monitor high levels of occupational benzene exposure. However, urinary phenol cannot be used to monitor low-level exposures. New biological indexes for exposure to low levels of benzene are thus needed. The aim of this study was to investigate the relations between exposure to benzene (Abenzene, ppm), as measured by personal air sampling, and the excretion of benzene (U-benzene, ng/l),trans,trans-muconic acid (MA, mg/g creatinine), andS-phenylmercapturic acid (PMA, g/g creatinine) in urine. The subjects of the study were 145 workers exposed to benzene in a chemical plant. The geometric mean exposure level was 0.1 ppm (geometric standard deviation = 4.16). After logarithmic transformation of the data the following linear regressions were found: log (U-benzene, ng/l) = 0.681 log (A-benzene ppm) + 4.018; log (MA, mg/g creatinine) = 0.429 log (A-benzen ppm) – 0.304; and log (PMA, g/g creatinine) = 0.712 log (A-benzene ppm) + 1.664. The correlation coefficients were, respectively, 0.66, 0.58, and 0.74. On the basis of the equations it was possible to establish tentative biological limit values corresponding to the respective occupational exposure limit values. In conclusion, the concentrations of benzene, mercapturic acid, and muconic acid in urine proved to be good parameters for monitoring low benzene exposure at the workplace.     

苯职业接触工人尿中酚和黏糠酸监测结果及意义

目的通过对苯接触工人尿中酚和反-反式黏糠酸的监测与分析,开展低苯环境下苯接触生物标志物研究,并探讨其实际应用价值。方法选取某制鞋厂员工作为研究对象,测定其尿液中酚和反-反式黏糠酸浓度,并对作业工人工作场所中苯浓度进行监测。结果接苯工人尿酚浓度与接苯浓度无显著性相关关系,尿中反-反式黏糠酸浓度与接苯浓度存在显著正相关(P0.05),接苯工人班后尿中的反-反式黏糠酸浓度显著高于班前尿(P0.05),吸烟对尿酚浓度影响较小,吸烟者尿中反-反式黏糠酸浓度显著高于非吸烟者(P0.05)。结论低浓度苯工作环境下,尿中反-反式黏糠酸可以作为一种敏感的生物标志物替代尿酚反映机体苯暴露情况。     

Urinary t,t-muconic acid as an indicator of exposure to benzene

A method for rapidly determining t,t-muconic acid (MA) by high performance liquid chromatography was developed and successfully applied to urine samples from 152 workers exposed to benzene (64 men, 88 women) and 213 non-exposed controls (113 men, 100 women). The MA concentrations in urine correlated linearly with time weighted average benzene concentrations in the breath zone air of workers. A cross sectional balance study showed that about 2% of benzene inhaled is excreted into the urine as MA. The MA concentrations in the urine of the non-exposed was below the detection limit (less than 0.1 mg/l) in most cases, and the 95% lower confidence limit of MA for those exposed to benzene at 5 ppm (5.0 mg/l as a non-corrected value) was higher than the 97.5%-tile values for the non-exposed (1.4 mg/l). In practice, it was possible to separate those exposed to 6-7 ppm benzene from the non-exposed by means of urine analysis for MA. The urinary MA concentration was suppressed by coexposure to toluene.     

Urinary t,t-muconic acid as an indicator of exposure to benzene.

A method for rapidly determining t,t-muconic acid (MA) by high performance liquid chromatography was developed and successfully applied to urine samples from 152 workers exposed to benzene (64 men, 88 women) and 213 non-exposed controls (113 men, 100 women). The MA concentrations in urine correlated linearly with time weighted average benzene concentrations in the breath zone air of workers. A cross sectional balance study showed that about 2% of benzene inhaled is excreted into the urine as MA. The MA concentrations in the urine of the non-exposed was below the detection limit (less than 0.1 mg/l) in most cases, and the 95% lower confidence limit of MA for those exposed to benzene at 5 ppm (5.0 mg/l as a non-corrected value) was higher than the 97.5%-tile values for the non-exposed (1.4 mg/l). In practice, it was possible to separate those exposed to 6-7 ppm benzene from the non-exposed by means of urine analysis for MA. The urinary MA concentration was suppressed by coexposure to toluene.     

职业性苯暴露反-反式粘糠酸生物接触限值研究

目的研究职业性苯暴露反．反式粘糠酸（t,t—MA）生物接触限值。方法实验室建立生产环境空气中苯浓度的气相色谱检测方法及作业工人尿中t,t—MA含量的高效液相色谱检测方法,并通过检测苯暴露现场工人8h苯暴露水平及班前、班后尿中t,t．MA含量,研究其相关性。结果苯暴露者班前、班后尿中t,t—MA含量与其苯暴露水平有明显的相关关系。班前y（mg／gCr）=0．924＋0．108X（me／m^3）,r=0．62,P〈0．01;班后y（mg／gCr）=2．103＋0．177X（mg／m^3）,r=0．791,P〈0．01。结论根据我国作业场所空气中苯的国家卫生标准,按回归方程推导出职业接触苯生物接触限值,推荐职业暴露苯的生物接触限值为工作班班后尿t,t．MA含量为3．0mg／gCr,下一班班前尿t,t．MA含量为1．5mg／gGr。     

Validation of biomarkers in humans exposed to benzene: urine metabolites

BACKGROUND: The present study was conducted among Chinese workers employed in glue- and shoe-making factories who had an average daily personal benzene exposure of 31+/-26 ppm (mean+/-SD). The metabolites monitored were S-phenylmercapturic acid (S-PMA), trans, trans-muconic acid (t,t-MA), hydroquinone (HQ), catechol (CAT), 1,2, 4-trihydroxybenzene (benzene triol, BT), and phenol. METHODS: S-PMA, t,t-MA, HQ, CAT, and BT were quantified by HPLC-tandem mass spectrometry. Phenol was measured by GC-MS. RESULTS: Levels of benzene metabolites (except BT) measured in urine samples collected from exposed workers at the end of workshift were significantly higher than those measured in unexposed subjects (P < 0.0001). The large increases in urinary metabolites from before to after work strongly correlated with benzene exposure. Concentrations of these metabolites in urine samples collected from exposed workers before work were also significantly higher than those from unexposed subjects. The half-lives of S-PMA, t,t-MA, HQ, CAT, and phenol were estimated from a time course study to be 12.8, 13.7, 12.7, 15.0, and 16.3 h, respectively. CONCLUSIONS: All metabolites, except BT, are good markers for benzene exposure at the observed levels; however, due to their high background, HQ, CAT, and phenol may not distinguish unexposed subjects from workers exposed to benzene at low ambient levels. S-PMA and t,t-MA are the most sensitive markers for low level benzene exposure.     

Evaluation of biomarkers for occupational exposure to benzene.

OBJECTIVE--To evaluate the relations between environmental benzene concentrations and various biomarkers of exposure to benzene. METHODS--Analyses were carried out on environmental air, unmetabolised benzene in urine, trans, trans-muconic acid (ttMA), and three major phenolic metabolites of benzene; catechol, hydroquinone, and phenol, in two field studies on 64 workers exposed to benzene concentrations from 0.12 to 68 ppm, the time weighted average (TWA). Forty nonexposed subjects were also investigated. RESULTS--Among the five urinary biomarkers studied, ttMA correlated best with environmental benzene concentration (correlation coefficient, r = 0.87). When urinary phenolic metabolites were compared with environmental benzene, hydroquinone correlated best with benzene in air. No correlation was found between unmetabolised benzene in urine and environmental benzene concentrations. The correlation coefficients for environmental benzene and end of shift catechol, hydroquinone, and phenol were 0.30, 0.70, and 0.66, respectively. Detailed analysis, however, suggests that urinary phenol was not a specific biomarker for exposure below 5 ppm. In contrast, ttMA and hydroquinone seemed to be specific and sensitive even at concentrations of below 1 ppm. Although unmetabolised benzene in urine showed good correlation with atmospheric benzene (r = 0.50, P < 0.05), data were insufficient to suggest that it is a useful biomarker for exposure to low concentrations of benzene. The results from the present study also showed that both ttMA and hydroquinone were able to differentiate the background level found in subjects not occupationally exposed and those exposed to less than 1 ppm of benzene. This suggests that these two biomarkers are useful indices for monitoring low concentrations of benzene. Furthermore, these two metabolites are known to be involved in bone marrow leukaemogenesis, their applications in biological monitoring could thus be important in risk assessment. CONCLUSION--The good correlations between ttMA, hydroquinone, and atmospheric benzene, even at concentrations of less than 1 ppm, suggest that they are sensitive and specific biomarkers for benzene exposure.     

Biological monitoring of exposure to low concentrations of styrene

A field study was conducted on 39 male workers exposed to styrene at concentrations below 40 ppm (time weighted average, TWA). Analyses were carried out on environmental air, exhaled air, blood, urine, and two major urinary metabolites of styrene: mandelic acid (MA) and phenylglycoxylic acid (PGA). Head space gas chromatography (GC) with a flame ionization detector (FID) was used for determination of styrene in blood and urine. Postexposure exhaled air was analyzed using capillary GC. Environmental styrene exposure was measured by personal sampling using carbon cloth personal samplers. Urinary metabolites of styrene were determined by high pressure liquid chromatograph (HPLC). When the end-of-shift breath, blood, and urine styrene levels were compared with environmental TWA values, blood styrene correlated best with styrene in air (r = 0.87), followed by breath styrene (r = 0.76). Poor correlation (r = 0.24) was observed between environmental styrene exposure and urine styrene. When styrene metabolites were compared with environmental styrene, the sum of urinary MA and PGA correlated better with styrene in air than MA or PGA alone. The correlations between urinary metabolites and environmental styrene improved when corrected for the specific gravity of urine. Even better correlations were observed when the urinary metabolites were corrected for creatinine. The correlation coefficients for environmental styrene and end-of-shift MA, PGA, and MA + PGA were 0.83, 0.84, and 0.86, respectively. The correlation coefficients between environmental styrene and next morning urinary metabolites fell to 0.47, 0.61, and 0.65 for MA, PGA, and MA + PGA, respectively. These results suggest that determination of the total MA and PGA in urine samples is preferred than separate measurements of MA or PGA. The good correlation between environmental exposure and styrene in the exhaled air also suggests that breath styrene level can be a useful indicator for low level styrene exposure, as the method is specific, noninvasive, and rapid. Urinary styrene seems to be a less reliable indicator for low level styrene exposure. © 1994 Wiley-Liss, Inc.