职业接触二甲苯尿中甲基马尿酸生物限值的研究

选择不同暴露水平的二甲苯接触个体,检测个体二甲苯暴露浓度,同时采集当日工人班末尿样,对尿中二甲苯的代谢产物甲基马尿酸的含量进行测定,将二甲苯的外暴露空气浓度与体内甲基马尿酸代谢量进行回归分析,结合国外限值资料,提出适合我国职业卫生现状的甲基马尿酸生物限值的建议。接触工人在空气中二甲苯浓度为0～144.21 mg/m3时,班末尿中甲基马尿酸(MHA)与空气中二甲苯浓度之间存在良好相关性,肌酐校正回归方程为y(g/g肌酐)=0.0052x(mg/m3)+0.0112,r=0.731;比重校正回归方程为y(g/L)=0.0089x(mg/m3)-0.0259,r=0.793。将我国二甲苯职业接触限值50 mg/m3分别代入回归方程,推出工作班末尿中甲基马尿酸含量为0.271 g/g肌酐和0.419 g/L。依据我国二甲苯实际接触情况,参考国外相关标准和文献,建议我国职业接触二甲苯的代谢产物尿中甲基马尿酸的生物接触限值为班末尿0.3 g/g肌酐或0.4 g/L。     

尿中马尿酸及甲基马尿酸的分离和测定

甲苯进入人体被醇脱氢酶氧化成苯甲醛,再经醛脱氢酶氧化成苯甲酸,苯甲酸与甘氨酸结合成马尿酸从尿中排出。二甲苯进入人体后,二个甲基中的一个被氧化,它同甲苯的代谢途径一样最后变为甲基马尿酸从尿中排出,不接触二甲苯者在一般的情况下尿中不含有甲基马尿酸,所以测定尿中甲基马尿酸有其特殊价值。关于测定尿中马尿酸及甲基马尿酸的方法和研究工作曾有报导。     

甲基马尿酸作为接触二甲苯生物监测指标的研究

进入体内的二甲苯95%经代谢后生成水溶性甲基马尿酸(MethyLhippuric acids.简称MHAs)从尿中排出,5%左右以原形从呼吸道排出。二甲苯的生物监测指标有血中二甲苯,呼出气中二甲苯和尿中MHAs等。尿中MHAs具有灵敏度高特异性强的特征,加之采样方便,可能是较有用的生物监测指标。我们研究职业接触二甲苯工人和志愿者尿中MHAs的排出,提示班末或整个接触期间尿中MHAs的排出     

气相色谱法测定尿中马尿酸和甲基马尿酸

甲苯与二甲苯溶剂在工业生产中应用较为广泛,因此作为职业接触甲苯、二甲苯工人的生物监测指标,分析尿中马尿酸与甲基马尿酸的排泄量,对评价二种溶剂经机体代谢情况,从而估计现场环境空气中化合物的浓度具有一定的意义。 已知甲苯进入机体后,大部被氧化成苯甲酸,与甘氨酸结合成马尿酸(HA)由尿中排出。二甲苯由三个异构体组成,以间位为主进入机体后,经生物转     

尿中甲基马尿酸与马尿酸薄层分离条件的比较和选定

为了评价甲苯、二甲苯在车间空气中的污染程度和工人的接触程度,采用薄层层析分离和测定尿中甲基马尿酸和马尿酸具有一定的参考价值,但分离效果不稳定。为使职业病检验工作能更好地为生产服务,做好劳动保护和职业病防治工作,我们对尿中甲基马尿酸和马尿酸的薄层分离条件进行了比较和选定。     

接触二甲苯后尿中甲基马尿酸排泄的动态变化

二甲苯常用作苯的代用品,多用于涂、烘漆作业。接触二甲苯后,可用其特异性的代谢产物甲基马尿酸,作为评价工人接触程度的指标。近年来许多学者在这方面作了较多的研究。为了选择甲基马尿酸测定的最佳留尿时间,我们对接触二甲苯后尿中甲基马尿酸的排泄规律,作了初步探讨。 对象与方法 三名男性志愿者,年龄24—26岁,在上海电磁线厂细丝车间跟班劳动。该厂主要生产漆包线,以二甲苯作为漆的溶剂。工艺过程为:铜丝进线→退火→上漆→烘干→成品。24小时连续生产,8小时一班。志愿者随同工人在不同操作地点和休息地点用针筒采集空气样品,以气相色谱法测定二甲苯的     

接触二甲苯工人尿中甲基马尿酸排泄动态的初步观察

二甲苯虽毒性较苯为低,但对工人仍有不良影响,故有效地监测二甲苯作业工人的吸收量,在劳动卫生工作中有实际意义。甲基马尿酸是二甲苯进入机体后的特异性代谢产物,我们分析测定了接触者尿中的甲基马尿酸,观察排泄与接触时间的关系,以及探讨应用     

HPLC法测定尿中马尿酸和甲基马尿酸

我们曾用薄层层析法测定尿中的马尿酸和甲基马尿酸。其法虽然简单,但点样和展开颇费时间,而且定量的准确度差。近年来有文献介绍用 HPLC 法测定尿中上述二种酸。作者参考了这些方法,以国产高压液相仪分离和测定上述二种酸。尿样萃取后直接进样,不必预先用重氮甲烷酯化。本法经过现场测定接触甲苯,二甲苯工人尿中的马尿酸和甲基马尿酸,结果说明以马尿     

尿中甲基甲酰胺作为二甲基甲酰胺接触者生物监测指标的探讨

本文分别检测了57名正常人和205名接触二基甲酰胺工人尿中甲基甲酰胺含量及空气中二甲基甲酰胺浓度．正常组空气二甲基甲酰胺浓度低于0．25mg／m3．尿中甲基甲酰胺末检出，接触组空气中二甲基甲酰胺平均浓度变为7．68±3．05mg／m3，工人班末尿中甲基甲酰胺平均含量为4．40±3．25mg／g肌酐．结果表明，班末尿中甲基甲酰胺含量及检出率与空气中二甲基甲酰胺浓度显著相关．班末尿中甲基甲酰胺含量能更客观地反映工人二甲基甲酰胺接触程度．因此它可作为甲基甲酰胺接触者一项有价值的生物监测指标．     

二甲苯接触者尿中代谢产物甲基马尿酸的测定研究

由于苯是严重的造血系统毒物,因此目前已采取很多低毒的代用品取代苯。二甲苯就是常用的一种代用品,多用于喷烘漆作业,二甲苯的毒性研究资料不多,对造血系统的作用说法也不一。近来发现甲基马尿酸是二甲苯进入人体以后的特异性代谢产物,并在二甲苯作业工人的尿中分离出甲基马尿酸,提出了定量测定方法,其测定结果可     

Biological monitoring of workers exposed to ethylbenzene and co-exposed to xylene

OBJECTIVE: Ethylbenzene is an important constituent of widely used solvent mixtures in industry. The objective of the present study was to provide information about biological monitoring of occupational exposure to ethylbenzene, and to review the biological limit values corresponding to the threshold limit value of ethylbenzene. METHODS: A total of 20 male workers who had been exposed to a mixture of ethylbenzene and xylene, through painting and solvent mixing with commercial xylene in a metal industry, were recruited into this study. Environmental and biological monitoring were performed during an entire week. The urinary metabolites monitored were mandelic acid for ethylbenzene and methylhippuric acid for xylene. Correlations were analyzed between urinary metabolites and environmental exposure for ethylbenzene and xylene. The interaction effects of a binary exposure to ethylbenzene and xylene were also investigated using a physiologically based pharmacokinetic (PBPK) model. RESULTS: The average environmental concentration of organic solvents was 12.77 ppm for xylene, and 3.42 ppm for ethylbenzene. A significant correlation (R2 = 0.503) was found between environmental xylene and urinary methylhippuric acid. Urinary level of methylhippuric acid corresponding to 100 ppm of xylene was 1.96 g/g creatinine in the worker study, whereas it was calculated as 1.55 g/g creatinine by the PBPK model. Urinary level of mandelic acid corresponding to 100 ppm of ethylbenzene was found to be 0.7 g/g creatinine. PBPK results showed that the metabolism of ethylbenzene was highly depressed by co-exposure to high concentrations of xylene leading to a non-linear behavior. CONCLUSIONS: At low exposures, both methylhippuric acid and mandelic acid can be used as indicators of commercial xylene exposures. However at higher concentrations mandelic acid cannot be recommended as a biological indicator due to the saturation of mandelic acid produced by the co-exposure to xylene.     

Excretion of methylhippuric acids in urine of workers exposed to a xylene mixture: comparison among three xylene isomers and toluene

Summary The correlation between exposure to three xylene isomers and resulting urinary excretion of corresponding methylhippuric acid (MHA) isomers was studied among 175 Chinese workers of both sexes who had been predominantly exposed to xylenes (exposure to xylenes accounting for 70% or more of the total exposure on a ppm basis). Nonexposed controls (281 men and women) were also studied to define the background level of MHAs in urine. The solvent exposure of xylene-exposed workers during their workshift was monitored by diffusive sampling of breathing zone air, and MHAs in shift-end urine were determined by high-performance liquid chromatography. Regression analysis showed that the concentration of each MHA isomer correlated significantly with the time-weighted average intensity of exposure to the corresponding xylene isomer, and therefore the correlation between the sum of three xylene isomers in air and that of three MHA isomers in urine was also significant; the slope of the regression line was essentially the same among the three isomers. The calculated regression line suggested that the urinary MHA level after hypothetical exposure to xylenes at 100 ppm will be somewhat less than the proposed biological exposure index and biological tolerance value. Two social habits of smoking and drinking in combination suppressed the conversion of xylenes to MHAs in male workers.     

Biological monitoring of workers exposed to ethylbenzene and co-exposed to xylene

Objective: Ethylbenzene is an important constituent of widely used solvent mixtures in industry. The objective of the present study was to provide information about biological monitoring of occupational exposure to ethylbenzene, and to review the biological limit values corresponding to the threshold limit value of ethylbenzene. Methods: A total of 20 male workers who had been exposed to a mixture of ethylbenzene and xylene, through painting and solvent mixing with commercial xylene in a metal industry, were recruited into this study. Environmental and biological monitoring were performed during an entire week. The urinary metabolites monitored were mandelic acid for ethylbenzene and methylhippuric acid for xylene. Correlations were analyzed between urinary metabolites and environmental exposure for ethylbenzene and xylene. The interaction effects of a binary exposure to ethylbenzene and xylene were also investigated using a physiologically based pharmacokinetic (PBPK) model. Results: The average environmental concentration of organic solvents was 12.77 ppm for xylene, and 3.42 ppm for ethylbenzene. A significant correlation (R²=0.503) was found between environmental xylene and urinary methylhippuric acid. Urinary level of methylhippuric acid corresponding to 100 ppm of xylene was 1.96 g/g creatinine in the worker study, whereas it was calculated as 1.55 g/g creatinine by the PBPK model. Urinary level of mandelic acid corresponding to 100 ppm of ethylbenzene was found to be 0.7 g/g creatinine. PBPK results showed that the metabolism of ethylbenzene was highly depressed by co-exposure to high concentrations of xylene leading to a non-linear behavior. Conclusions: At low exposures, both methylhippuric acid and mandelic acid can be used as indicators of commercial xylene exposures. However at higher concentrations mandelic acid cannot be recommended as a biological indicator due to the saturation of mandelic acid produced by the co-exposure to xylene. Received: 6 March 2000 / Accepted: 10 June 2000     

Biological monitoring of low level occupational xylene exposure and the role of recent exposure

The correlation between low level time-weighted average (TWA) atmospheric xylene exposure (p.p.m.) and urinary methylhippuric acid (MHA) expressed per gram of creatinine was examined. Subjects were recruited from workplaces that utilized xylene. Ambient monitoring of o-, m- and p-xylene isomers was carried out using passive diffusion vapour monitors. Adjusted (post-shift minus pre-shift) and post-shift urinary levels of xylene metabolites (2-, 3- and 4-MHA) were determined by GC-MS. Twenty subjects were recruited into the study. Total xylene TWA exposures were 3.36 +/- 3.63 p.p.m. (mean +/- SD) with a range of 0.03-14.44 p.p.m. The r(2) values for the regression equations between xylene exposure and individual and total adjusted MHA isomers were 0.390, 0.709, 0.677 and 0.631 for o-, m-, p- and total xylenes, respectively, which was greater than the respective correlations between non-adjusted samples. In conclusion, biological monitoring of occupational xylene exposure at levels <15 p.p.m. using urinary MHA showed a good correlation with atmospheric levels and is a valid complement to ambient monitoring. Even though occupational xylene exposure in the workplaces studied was generally low, MHA was found in the pre-shift urine of all workers and the use of adjusted values showed modest improvements in correlations. Recent exposure prior to sampling, either from occupational or non-occupational sources, should be considered when biological monitoring of xylene is undertaken. Extrapolation of data from this study predicted a MHA concentration in post-shift urine of 1.3 g/g creatinine after exposure to a TWA of 100 p.p.m. xylene.     

Exposure of workers to a mixture of toluene and xylenes. I. Metabolism.

The urinary excretion of hippuric acid and methylhippuric acid was studied in workers (233 subjects; 122 men and 111 women) exposed to toluene and xylenes in combination and in non-exposed controls (281 subjects; 141 men and 140 women) recruited from the same factories or factories of the same regions. Smoking and drinking habits of the subjects were obtained by medical interviews. From each worker, one urine sample was collected at the end of a shift and analysed for hippuric and methylhippuric acids by high performance liquid chromatography. Air samples for the estimation of toluene and xylenes were collected with diffusive personal samplers. There was a linear correlation between the time weighted average exposure either to toluene or xylene isomers and the concentrations of hippuric acid or methylhippuric acid isomers in urine. Essentially no difference was found in the correlation between quantitative exposure and excretion in the three xylene isomers. Comparison of the slopes of regression lines indicated the absence of metabolic interaction between toluene and xylenes at the measured concentrations. The metabolism of toluene and xylenes was significantly reduced among smokers or drinkers compared with non-smokers and non-drinkers.     

Dermal absorption of solvents as a major source of exposure among shipyard spray painters

OBJECTIVE: The purpose of this study was to evaluate the relevance of inhalational and dermal exposure to solvents in shipyard spray painters. Special emphasis was placed on the spatial distribution of dermal exposure and absorption across different regions of the body. METHODS: Fifteen male spray painters were recruited for this study. The subjects were monitored during a 3-day work period using a repeated-measures study design. Air and dermal exposure of solvents were collected each day. Urine was collected before and after the work shift. RESULTS: Air samples showed that the workers were primarily exposed to ethylbenzene and xylene. The concentrations of ethylbenzene and xylene outside the workers' masks were 59.2 +/- 10.4 (mean +/- standard error [SE]) ppm and 29.4 +/- 4.70 ppm, whereas those inside the masks were 7.91 +/- 17.4 ppm and 3.83 +/- 8.22 ppm, respectively. The average mass of ethylbenzene and xylene across the different body regions inside the block units of assembled ships were 305.1 +/- 63.9 mg and 165.6 +/- 34.1 mg. The quantity was, on average, 5.8 and 5.1 times higher than those collected outside the blocks. In both measurements, the highest exposure mass was found on the upper legs, and the lowest exposure mass was found on the back. Principal component analysis (PCA) was used to transform the variables of dermal exposure for all investigated body regions into only one principal component. Multiple regression analyses revealed a significant relationship between dermal exposure to xylene (PCA dermal xyl) and urinary methylhippuric acid (MHA) levels, adjusting for air xylene exposure (R2=0.491, P<0.05). CONCLUSIONS::The present study indicated that dermal exposure to xylene significantly increased the urinary levels of MHA, suggesting that dermal exposure to solvents was an important route among spray painters.     

Urinary methylhippuric acid isomer levels after occupational exposure to a xylene mixture

Summary The quantitative relationship between exposure to xylene vapor and urinary excretion of methylhippuric acid (MHA) isomers were studied in the second half of a working week. The participants in the study were 121 male workers engaged in dip-coating of metal parts who were predominantly exposed to three xylene isomers. The intensity of exposure measured by diffusive sampling during an 8-h shift was such that the geometric mean vapor concentration was 3.8 ppm for xylenes (0.8 ppm for o-xylene, 2.1 ppm for m-xylene, and 0.9 ppm for p-xylene), 0.8 ppm for toluene, and 0.9 ppm for ethylbenzene. Urine samples were collected at the end of the shift and analyzed for metabolities by HPLC. The statistical analysis showed that there is a linear relationship between the intensity of exposure to xylenes and the concentration of MHA in urine, that the regression line passes very close to the origin, and that the increment in observed (i.e., noncorrected) MHA concentrations as a function of increasing xylene concentration was 17.8 mg × 1^–1 ppm^–1. Further examination on the basis on individual xylene isomers showed that the slopes of the regression lines for o- and m-isomers were similar (i.e., 17.1 and 16.6 mg l^–1 ppm^–1, respectively), whereas that for p-xylene was larger (21.3 mg l^–1 ppm^–1).     

Aromatic and polycyclic hydrocarbons in air and their urinary metabolites in coke plant workers

This study describes the exposure of coke plant workers to hydrocarbons. Aromatic hydrocarbons (AHs) and polycyclic aromatic hydrocarbons (PAHs) in the breathing zone air and their oxygenated metabolites in the urine of coke plant workers are qualitatively and quantitatively determined. Concentrations of benzene, toluene, naphthalene, m+p-xylene, o-xylene and 14 different PAHs were measured at the different workplaces by personal air sampling. O-cresol, 1- and 2-naphthol, methylhippuric acid, and 1-hydroxypyrene were determined in hydrolyzed urine of workers collected after the work shift. The gas chromatography–mass spectrometry (GC/MS) method was applied to identify AHs in air and in urine samples. Time-weighted values of exposure to aromatic hydrocarbons at a coke plant were: benzene (0.06–9.82 mg/m³), toluene (0.05–4.71 mg/m³), naphthalene (0.01–3.28 mg/m³), o-xylene (0.01–1.76 mg/m³) and m + p-xylene (0.01–2.62 mg/m³). At the coke batteries, the total concentration of PAHs ranged from 7.27 to 21.92 μg/m³. At the sorting department, the total concentration of PAHs were about half this value. Concentration of the urinary metabolites (naphthols and methylhippuric acid) detected in workers at the tar distillation department are three times higher than those for the coke batteries and sorting department workers. A correlation between inhaled toluene, naphthalene, xylene, and urinary excretion of metabolites has been found. Time-weighted average concentrations of AHs in the breathing zone air show that exposure levels of the workers are rather low in comparison to exposure limits. The 1-hydroxypyrene concentration is below 24.75 μmol/mol creatinine. The GC/MS analysis reveals the presence of AHs, mainly benzene and naphthalene homologues. It has been found that coke plant workers are simultaneously exposed to the mixture of aromatic and polycyclic hydrocarbons present in the breathing zone air of a coke plant. Exposure levels are significantly influenced by job categories. Compounds identified in the urine appear to be the products of the hydroxylation of AHs present in the air as well as unmetabolized hydrocarbons. Am. J. Ind. Med. 34:445–454, 1998. © 1998 Wiley-Liss, Inc.     

Percutaneous absorption of m-xylene in man

Summary Percutaneous absorption of m-xylene was studied in volunteer experiments by means of monitoring xylene concentrations in blood and in exhaled air, and urinary methylhippuric acid excretion. Compared to normal working practices a rather extreme skin exposure, i.e. immersion of both hands in liquid xylene resulted in an estimated absorption of 35 mg xylene in 15 min which equals an estimated pulmonary retention within the same time period at TLV air.level of 100 ppm. The observed absorption rate for m-xylene was approximately 2 g/cm²/min. The penetration of xylene was fairly rapid, peak concentrations appearing in the draining venous blood 4–6 min after exposure. Further absorption took place for five hours, however, after the termination of exposure and the removal of the contaminant by alcohol and water rinsing. It was found, as expected, that venous blood from a contaminated area exhibits a much higher concentration of the contaminant than mixed venous blood. To exclude this error in biological monitoring of xylene (and other skin penetrating solvents) exposure, exhaled air determinations are recommended. As a sporadic finding in the investigation, a symptom-free subject with previous history of atopic dermatitis developed toxic eczema of the hands after xylene exposure and exhibited a three times greater absorption of the compound than the average for the rest of the group.     

甲苯的慢性危害和尿中的马尿酸作为职业性接触的生物学监测指标探讨

本文对１４０名接触以甲苯为主的有机溶剂的包漆工（平均接触工龄８．３９年）进行了横断面调查，发现头昏、头痛、失眠、乏力、腹隐痛等症状的出现率，神衰综合征和慢性咽炎的患病率明显高放对照组（Ｐ＜０．０５或Ｐ＜０．０１）。常规肝功能和血清碱性磷酸酶（Ｓ－ＡＫＰ）无明显改变（Ｐ＞０．０５）。包漆工班末尿马尿酸平均浓度显著高於班前和对照组班末的平均浓度（分别Ｐ＜０．０５，Ｐ＜０．０１）。男、女包漆工班末尿马尿酸平均浓度均高于班前（分别Ｐ＜０．０５，Ｐ＜０．０１）。空气中苯系物的浓度均在最高允许浓度范围内。结果提示，长期接触低浓度的以甲苯为主的有机溶剂，对中枢神经系统有不利影响。尿中马尿酸水平可作为反映工人接触低浓度甲苯的有用的、生物学监测指标。