呼出苯和血苯作为生物接触指标的研究

对两皮鞋厂的３０名（男１１名，女１９名）苯作业工人，分别监测其呼出苯、血苯、尿酚浓度和车间空气苯以及呼出苯的毒代动力学观察。结果表明各指标间都有明显的正相关（Ｐ＜０．０１）和好的线性关系。班前呼出苯分别为０．０２６（停止接触４０ｈ）和０．１３６ｍｇ／ｍ３（停止接触１６ｈ）；血苯班前班后平均浓度分别为３．２ｌ和１０μｇ／Ｌ；班前班后血／气分配系数分别为６．６７和７．６０。１６ｈ衰减率达９９％以上。故以呼出苯和血苯作为职业性苯接触的生物监测指标，简便、灵敏、特异性好。     

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。     

苯接触与尿中反-反式黏糠酸和苯巯基尿酸关系研究

目的探讨职业苯接触与尿中反-反式黏糠酸(ttMA)和苯巯基尿酸(SPMA)的相关性,评定两接触标志物作为生物监测指标的适用性。方法对44名制鞋厂接苯工人进行个体苯暴露水平的作业环境监测,采集当日班前与班后尿样,分别用高效液相色谱和液质联谱测定尿中ttMA和SPMA含量。结果个体苯接触浓度为2.57~146.11 mg/m3,几何平均浓度为(27.91±3.29)mg/m3。班后尿中ttMA和SPMA含量均较班前增高,差异有统计学意义(P0.01),班后ttMA和SPMA与空气苯浓度的相关系数分别为0.905(P0.01)和0.537(P0.01),个体苯接触代谢转化为ttMA和SPMA的相对内暴露指数(RIE)随苯接触浓度的增高而下降。结论在中、高浓度的苯接触时,班后尿ttMA与空气苯浓度的相关性优于SPMA。     

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。     

苯接触人群的生物标志物研究进展

苯是应用广泛的化工原料.接触苯可引起急、慢性苯中毒,甚至白血病.研究苯接触人群的生物标志物在了解苯致病机制、接触苯人群的健康筛查等方面有重要价值,下面就国内外关于苯接触人群的生物标志物的研究进行综述. 1 苯的接触标志物 接触标志物是指进入机体内的外源性物质、代谢产物和它们与靶分子交互作用的产物.苯进入人体后多储留在脂肪组织内,在肝脏氧化成苯环氧化物,环氧化物与谷胱甘肽结合,形成苯巯基尿酸(S-PMA),其半减期为12.8 h[1].PACI等[2]利用高效液相色谱-串联质谱联用(HPLC/MS/MS)对S-PMA进行了研究,得到了尿S-PMA与苯的时间加权平均浓度直线相关,且不受性别、年龄、吸烟习惯的影响.     

苯作业者呼出苯的生物学监测

苯作业者呼出苯的生物学监测刘庆宪（上海市卢湾区卫生防疫站，上海２０００２５）利用呼出苯作为生物学监测指标，对接触水平和接触者可能受到的有害影响进行卫生学评价，为此我们对苯作业者的呼出苯排出动态及其与空气苯浓度、苯的代谢产物——尿酚的关系作了研究探讨。...     

苯接触者肺泡气毒物动力学研究

对接触不同浓度苯的工人70名(男45,女25)与志愿者9名(男) (?)续观察其工作接触后肺泡气中苯浓度的变化,分析苯经呼气排出规律。经毒物动力学校型分析,三室模(?)拟合良好,半衰期分别为1.24min,21.17min及2.5h。苯经呼气排出的速率男女工间无明显差异,随接触浓度高低变化甚小:志愿者吸入苯的排出较快。接触浓度为30mg/m~3时的呼气苯排出的动力学方程为Ct=11.45e~(-0.558t) 1.058×e~(-0.03271) 4.95e~(-0.00466(?));并提出肺泡气苯浓度的生物接触指数建议值:班末:17.46mg/m~3,班后30min:4.70mg/m~3。     

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。     

苯接触工人的生物标志物的研究

长期低度度苯接触不仅影响骨髓造血功能,且已确认与白血病的发病有关.我国现行生产环境空气中苯的最高容许浓度(MAC)为40 mg/m3.发达国家已将苯接触阈限值-时间加权平均浓度(TLV-TWA)降至32 mg/m3(10 ppm)以下,美国的TLV从32 mg/m3降低为0.32 mg/m3[1].本文以生产环境中空气苯浓度与接触者血苯、尿酚和尿苯基硫醚氨酸的测定结果,进行该三项苯接触生物学标志物的分析,探索其实际应用价值.     

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。     

Benzene in the blood and breath of normal people and occupationally exposed workers

Benzene was measured in blood and alveolar air of 168 men, aged 20-58 years, subdivided into four groups: blood donors, hospital staff, chemical workers occupationally exposed to benzene, and chemical workers not occupationally exposed to benzene. The group of exposed workers was employed in work places with a mean environmental exposure to benzene of 1.62 mg/M3 (8 hr TWA). Non-exposed workers were employed elsewhere in the same plant, with an environmental exposure to benzene lower than 0.1 mg/M3. Blood and alveolar air samples were collected in the morning, before the start of the work shift for the chemical workers. The group of exposed workers was found to be significantly different from the other three groups, both for blood and alveolar benzene concentrations. The mean blood benzene concentration was 789 ng/l in the exposed workers, 307 ng/l in the non-exposed workers, 332 ng/l in the hospital staff, and 196 ng/l in the blood donors. Apart from the exposed workers, blood benzene concentration was significantly higher in smokers than in non-smokers. The mean alveolar benzene concentration was 92 ng/l in the exposed workers, 42 ng/l in the non-exposed workers, 22 ng/l in the hospital staff, and 11 ng/l in the blood donors. Alveolar benzene concentration was significantly higher in smokers than in non-smokers in the groups of the hospital staff and non-exposed workers, but not in the blood donors and exposed workers. In the three groups without occupational exposure considered altogether, the alveolar benzene concentration correlated significantly with environmental benzene concentration measured at the moment of the individual examinations, both in the smokers (r = .636; p less than .001) and non-smokers (r = .628; p less than .001). In the same three groups and in the exposed workers, alveolar benzene concentration showed a significant correlation with the blood benzene concentration.     

Lack of Sensitivity of Urinary Trans,Trans, -Muconic Acid in Determining Low-Level (ppb) Benzene Exposure in Children

Benzene is a widespread pollutant of which the main source in the outside environment is automotive traffic. Benzene is also present in cigarette smoke, and small quantities exist in drinking water and food; all of these sources contribute to pollution of indoor environments. Benzene exposure may be studied with biologic indicators. In the present study, the authors evaluated whether differences in urinary concentrations of trans, trans-muconic acid (t,t-MA) were detectable in a sample of 150 children and if the chemical was correlated with environmental exposures to low levels of benzene. The children attended primary schools that had significantly different—but low—environmental benzene levels. Analysis of urinary t,t-MA was achieved with high-performance liquid chromatography (photodiode array detector), and analysis of passive air samplers for benzene was performed with gas chromatography-mass spectrometry. Statistical analysis (Kruskal-Wallis test) indicated that differences in urinary levels of t,t-MA in children from urban and rural areas were not statistically significant (p = .07), nor were there significant differences between children with and without relatives who smoked (p = .69). As has been shown in other studies of children and adults, results of our study evidenced (1) the difficulty of correlating concentrations of urinary biomarkers with environmental exposure to benzene at a parts-per-billion level (i.e., traffic and environmental tobacco smoke) and, consequently, (2) the lack of specificity of t,t-MA as a biological indicator for the study of a population's exposure.     

苯接触评估:BAYES统计学的应用研究

[目的]用BAYES统计学方法估算车间空气中挥发性气体的区域浓度并检验其正确性。[方法]以某橡胶厂车间空气中苯浓度的历史监测资料为基础,结合专家主观概率及物理模型,进行BAYES统计推断,估算各岗位的区域浓度,并以现场测定数据对评估结果进行检验。[结果]估算的区域浓度最高的3个岗位为打浆、夹布机成型、搪浆;有7个岗位的区域浓度估算结果与8个岗位的现场采样结果无明显差别,而历史测量资料只有4个岗位的估算结果与现场采样结果无差别。[结论]BAYES统计学方法能降低变异,更有效地评估车间空气中挥发性有机物的区域浓度水平。     

Evidence That Humans Metabolize Benzene via Two Pathways

Background

Recent evidence has shown that humans metabolize benzene more efficiently at environmental air concentrations than at concentrations > 1 ppm. This led us to speculate that an unidentified metabolic pathway was mainly responsible for benzene metabolism at ambient levels.

Objective

We statistically tested whether human metabolism of benzene is better fitted by a kinetic model having two pathways rather than one.

Methods

We fit Michaelis-Menten-like models to levels of urinary benzene metabolites and the corresponding air concentrations for 263 nonsmoking Chinese females. Estimated benzene concentrations ranged from less than 0.001 ppm to 299 ppm, with 10th and 90th percentile values of 0.002 ppm and 8.97 ppm, respectively.

Results

Using values of Akaike’s information criterion obtained under the two models, we found strong statistical evidence favoring two metabolic pathways, with respective affinities (benzene air concentrations analogous to K_m values) of 301 ppm for the low-affinity pathway (probably dominated by cytochrome P450 enzyme 2E1) and 0.594 ppm for the high-affinity pathway (unknown). The exposure-specific metabolite level predicted by our two-pathway model at nonsaturating concentrations was 184 μM/ppm of benzene, a value close to an independent estimate of 194 μM/ppm for a typical nonsmoking Chinese female. Our results indicate that a nonsmoking woman would metabolize about three times more benzene from the ambient environment under the two-pathway model (184 μM/ppm) than under the one-pathway model (68.6 μM/ppm). In fact, 73% of the ambient benzene dose would be metabolized via the unidentified high-affinity pathway.

Conclusion

Because regulatory risk assessments have assumed nonsaturating metabolism of benzene in persons exposed to air concentrations well above 10 ppm, our findings suggest that the true leukemia risks could be substantially greater than currently thought at ambient levels of exposure—about 3-fold higher among nonsmoking females in the general population.     

Benzene and lymphohematopoietic malignancies in humans

BACKGROUND: Quantitative evaluations of benzene-associated risk for cancer have relied primarily on findings from a cohort study of highly exposed U.S. rubber workers. An epidemiologic investigation in China (NCI/CAPM study) extended quantitative evaluations of cancer risk to a broader range of benzene exposures, particularly at lower levels. METHODS: We review the evidence implicating benzene in the etiology of hematopoietic disorders, clarify methodologic aspects of the NCI/CAPM study, and examine the study in the context of the broader literature on health effects associated with occupational benzene exposure. RESULTS: Quantitative relationships for cancer risk from China and the U.S. show a relatively smooth increase in risk for acute myeloid leukemia and related conditions over a broad dose range of benzene exposure (below 200 ppm-years mostly from the China study and above 200 ppm-years mostly from the U.S. study). CONCLUSIONS: Risks of acute myeloid leukemia and other malignant and nonmalignant hematopoietic disorders associated with benzene exposure in China are consistent with other information about benzene exposure, hematotoxicity, and cancer risk, extending evidence for hematopoietic cancer risks to levels substantially lower than had previously been established. Published 2001 Wiley-Liss, Inc.     

接触苯作业工人白细胞计数限值的探讨

目的探讨接触苯作业工人职业健康检查中白细胞计数限值的利弊。方法对北京市某区2009—2010年职业健康检查资料进行回顾性分析。结果 57家各类企业的苯作业工人(2772人次)在岗期间体检中无症状性白细胞计数低于4.5×109/L者占8%,经复查及职业病诊断资质的医疗机构定期观察后,除4人(白细胞计数在4.1～4.4之间)外,其他确定无异常;同期,共计4247人参加接触苯作业上岗前体检,其中白细胞计数低于4.5×109/L者占8.6%,与前一数据相近。结论应将接触苯作业工人职业健康检查中白细胞计数的接触限值回归到4.0×109/L,以保护在岗工人及求职者的就业权。     

Benzene in environmental air and human blood

To study the blood benzene levels resulting from environmental and occupational benzene exposure. Methods: Benzene in venous blood was measured in 243 nonoccupationally exposed subjects (“normal” people) and in 167 workers occupationally exposed to benzene. All exposed workers gave blood samples at the end of the work shift and on the following morning before resuming work. Blood benzene was assayed by gas chromatography (GC)-mass spectrometry. Occupational benzene exposure was monitored by environmental personal samplers and measured by GC analysis. Results: The mean occupational benzene exposure for all 167 workers studied was 186 ng/l (58 ppb; range 5–1535 ng/l, 2–500 ppb). Overall, the mean blood benzene level of all workers was 420 ng/l at the end of the shift and 287 ng/l on the morning thereafter. The blood benzene levels measured the morning after turned out to be significantly lower (t = 3.6; P < 0.0001) than those measured at the end of the shift. The mean blood benzene level of the 243 “normal” subjects was 165 ng/l, which was significantly lower than that measured in the workers on the morning thereafter (t=5.8; P < 0.0000001). The mean blood benzene concentration was significantly higher in smokers than in nonsmokers in both the general population (264 versus 123 ng/l) and in the exposed workers. In the group of nonsmoking workers, whose workplace exposure to benzene was lower than 100 ng/l, blood benzene levels were similar (210–202 ng/l) to those measured in the nonsmoking general population (165 ng/l). End-of-shift blood benzene correlated significantly with environmental exposure (y=0.91x + 251; r=0.581; n=162; P < 0.00001). Finally, there was also a significant correlation between blood benzene measured at the end of the shift and that determined on the morning thereafter (y=0.45x + 109; r=0.572; n=156; P < 0.00001). Conclusion: Nonsmoking workers occupationally exposed to benzene at environmental levels lower than 100 ng/l (mean 35 ng/l) and the nonsmoking general population exposed to ubiquitous benzene pollution have similar blood benzene concentrations. This suggests that it is impossible to distinguish between occupational and environmental exposure when the benzene level in the workplace is less than 100 ng/l. Received: 31 December 1997 / Accepted: 4 August 1998     

室内空气中苯系物的溶剂解析气相色谱法测定

[目的]通过实验检测溶剂解析气相色谱法测定室内空气中苯系物的有效性。[方法]采用活性炭管吸附空气中苯系物,经二硫化碳解析后通过气相色谱（DB．FFAP色谱柱,FID检测器）检测苯系物浓度。[结果]苯、甲苯、乙苯、邻二甲苯、间二甲苯、对二甲苯在DB-FFAP色谱柱上分离良好,标准曲线的线性相关系数均为0．9999,质控样品浓度在标样定值范围内,相对标准偏差为0．55％～0．87％,样品平均解析效率为90．5％～101．5％。某用户新装修房屋的卧室、客厅及书房等室内二甲苯浓度均超过0．20mg／m^3,苯、甲苯、乙苯浓度较低。[结论]溶剂解析气相色谱法准确性好,适用于室内空气中苯系物的浓度测定。     

苯的两种生物标志物现场应用价值的比较

选择了８６名苯接触工人进行现场研究。结果表明当空气苯浓度的几何均值为３１．８６ｍｇ／ｍ３时，代谢物粘康酸的几何均值为３．１５３ｍｇ／ｇ，尿酚则为３１．０２７ｍｇ／ｇ。接触的空气苯浓度分别与代谢物粘康酸和尿酚之间的相关系数为０．９０１２、０．７３０１。接触低浓度苯的人群尿酚与外接触的苯水平相关性较差；但粘康酸无论是在接触高的或低的苯浓度情况下，二者之间均有良好的相关性。粘康酸在对照组检出水平极低。提示：粘康酸可替代尿酚作为苯的生物学监测指标     

长期低浓度苯接触的遗传损伤作用

［目的］ 探讨长期低浓度苯接触的遗传损伤作用。 ［方法］ 采用气相色谱法检测和评价工作场所空气中苯浓度;对苯接触组116 人和对照组62 人进行血常规检测、外周血淋巴细胞染色体畸变分析以及微核率检测。 ［结果］工作场所空气中苯浓度为〈0.033~1.898 mg/m3,低于我国苯职业接触限值［时间加权平均容许浓度（PC-TWA）=6 mg/m3;短时间接触容许浓度（PC-STEL）=10 mg/m3）］。苯接触组白细胞计数为（4.70±1.02）×109/L,低于对照组的白细胞计数（6.58±1.61）×109/L,差异有统计学意义（P 〈 0.01）,且与苯接触工龄呈负相关（r=-0.993,P 〈 0.01）;苯接触组和对照组染色体畸变率分别为（0.58±0.88）%和（0.13±0.42）%,微核率分别为（4.03±3.31）‰和（2.00±2.00）‰,该两项指标在苯接触组和对照组之间的差异均有统计学意义（P 〈 0.05）,且均与苯接触工龄呈正相关（r=0.289、0.616,P 〈 0.01）,与白细胞计数呈负相关（r=-0.306、-0.645,P 〈 0.01）。 ［结论］ 长期低浓度苯接触可造成细胞遗传损伤。