Excretion of 1,2,4-benzenetriol in the urine of workers exposed to benzene

Urine samples were collected from 152 workers (64 men, 88 women) who had been exposed to benzene, 53 workers (men only) exposed to a mixture of benzene and toluene, and 213 non-exposed controls (113 men, 100 women). The samples were analysed for 1,2,4-benzentriol (a minor metabolite of benzene) by high performance liquid chromatography. The time weighted average solvent exposure of each worker was monitored by diffusive sampling technique. The urinary concentration of 1,2,4-benzentriol related linearly to the intensity of exposure to benzene both in men and women among workers exposed to benzene, and was suppressed by toluene co-exposure among male workers exposed to a mixture of benzene and toluene. A cross sectional balance study in men at the end of the shift of a workday showed that only 0.47% of benzene absorbed will be excreted into urine as 1,2,4-benzenetriol, in close agreement with previous results in rabbits fed benzene. The concentration of 1,2,4-benzenetriol in urine was more closely related to the concentration of quinol than that of catechol. The fact that phenol and quinol, but not catechol, are precursors of 1,2,4-benzentriol in urine was further confirmed by the intraperitoneal injection of the three phenolic compounds to rats followed by urine analysis for 1,2,4-benzenetriol.     

Determination of catechol and quinol in the urine of workers exposed to benzene.

Time weighted average concentrations of benzene in breathing zone air (measured by diffusive sampling coupled with FID gas chromatography) and concentrations of catechol and quinol in the urine (collected at about 1500 in the second half of a working week and analysed by high performance liquid chromatography) were compared in 152 workers who were exposed to benzene (64 men, 88 women). The concentration of urinary metabolites was also determined in 131 non-exposed subjects (43 men, 88 women). There was a linear relation between the benzene concentrations in the breathing zone and the urinary concentrations of catechol and quinol (with or without correction for urine density) in both sexes. Neither catechol nor quinol concentration was able to separate those exposed to benzene at 10 ppm from those without exposure. The data indicated that when workers were exposed to benzene at 100 ppm about 25% of benzene absorbed was excreted into the urine as phenolic metabolites, of which 13.2%, 1.6%, and 10.2% are phenol, catechol, and quinol, respectively.     

Determination of catechol and quinol in the urine of workers exposed to benzene

Time weighted average concentrations of benzene in breathing zone air (measured by diffusive sampling coupled with FID gas chromatography) and concentrations of catechol and quinol in the urine (collected at about 1500 in the second half of a working week and analysed by high performance liquid chromatography) were compared in 152 workers who were exposed to benzene (64 men, 88 women). The concentration of urinary metabolites was also determined in 131 non-exposed subjects (43 men, 88 women). There was a linear relation between the benzene concentrations in the breathing zone and the urinary concentrations of catechol and quinol (with or without correction for urine density) in both sexes. Neither catechol nor quinol concentration was able to separate those exposed to benzene at 10 ppm from those without exposure. The data indicated that when workers were exposed to benzene at 100 ppm about 25% of benzene absorbed was excreted into the urine as phenolic metabolites, of which 13.2%, 1.6%, and 10.2% are phenol, catechol, and quinol, respectively.     

Genotoxic effects in peripheral blood and urine of workers exposed to low level benzene.

Blood samples were obtained from a population of refinery workers representing different age groups. Sixty six men with low average exposure to benzene and 33 male controls were investigated. An examination of cell cycle kinetics and sister chromatid exchange was carried out on control and exposed individuals. No significant differences were found between groups of individuals varying in their drinking and smoking habits or their exposure to diagnostic x rays. Individuals with the lowest and highest phenol values were examined for urine mutagenicity, with urinary phenol used here as an indicator of benzene exposure. There was no difference in the number of revertant colonies in strains TA98 and 100 between the high and low urinary phenol groups. There were also no differences in any of the biochemical measures or haematological parameters investigated in all the individuals except that higher values for mean corpuscular volume were found in exposed than in control individuals. These values, however, were within the normal clinical range.     

职业接触苯工人尿中黏糠酸测定方法与生物限值研究

目的推荐我国职业接触苯尿中反-反式黏糠酸（uMA）生物限值并建立相应的高效液相色谱（HPLC）测定方法。方法选择职业苯接触者56人和非苯接触者24人，应用活性炭吸附管采集工人呼吸带空气、CS2洗脱、毛细管气相色谱法检测个体外暴露水平，同时采集当日工作班前和班末尿样本，应用HPLC测定尿中uMA以观察内暴露水平。尿样经2mol／L盐酸酸化、香草酸为内标、乙酸乙酯萃取预处理，采用ODS柱、冰乙酸：四氢呋喃：甲醇：水（体积比1：2：10：87）为流动相、流速0．9ml／min、紫外检验波长264nm、柱温25℃的色谱条件分离测定尿中uMA。结果uMA的线性范围为0．10～10．00mg／L，检出限为0．10mg／L，加标平均回收率为95．1％～100．5％，批内、批间精密度变异系数分别为4．4％～7．5％和6．2％～8．8％。接苯工人空气苯浓度范围0．332～146．000mg／m^3，平均浓度41．8mg／m^3，班末尿uMA与个体苯接触量存在良好线性关系y（mg／gCr）=2．103＋0．177x（mg／m^3），r=0．791，P〈0．01，将我国职业苯接触限值PC—TWA=6mg／m^3代入回归方程，推算工作班末尿中uMA含量为3．165mg／gCr。结论建立的HPLC测定uMA方法简便、快速、灵敏，可用于职业接触苯的生物监测，参考国内外文献和国外相关标准，建议我国职业接触苯生物限值班末尿uMA为2．4mmol／molCr（3．0mg／gCr）。     

Muconic acid determinations in urine as a biological exposure index for workers occupationally exposed to benzene.

Urinary phenol determinations have traditionally been used to monitor high levels of occupational benzene exposure, but the same technique cannot be used to monitor low-level exposures because of the high background of phenol resulting from its presence in many foods and from metabolism of aromatic amino acids. Thus, new biological indexes for exposure to low levels of benzene are needed. Animal studies indicate that muconic acid is a metabolite of benzene that is excreted in the urine as an increasing fraction of the total benzene metabolites with decreasing dose of benzene. Thus, urinary muconic acid is potentially useful as a monitor for low levels of exposure to benzene. It is also of interest to determine the level of muconic acid in the urine of humans exposed to benzene for comparison with animal data as an aid for use of the animal studies in risk assessments for humans. This report describes the development of a gas chromatography/mass spectrometry assay to detect and quantitate the benzene metabolite, muconic acid, in urine. The internal standard used in the assay, muconic acid-d4, was biosynthesized by F344/N rats administered benzene-d6 by gavage; the muconic acid was isolated from the rat's urine. Muconic acid was measured in experimental urine samples by adding the internal standard, followed by extraction and derivatization. Phenol was also measured in urine after extraction and derivatization. The assays were applied to the urine samples from 14 workers occupationally exposed to benzene and 8 workers with no known benzene exposure. Muconic acid could be detected in all of the urine samples at levels greater than 100 ng/mL.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cytogenetic study of workers exposed to benzene

Cytogenetic evaluation of peripheral lymphocytes from 52 workers exposed to low levels of benzene (less than 10 ppm) has revealed an increase in aberration rates as compared to that of a 44-person group seen for preemployment examination. Statistically significant differences were found in the distribution of specific types of chromosomal aberrations. These induced-aberrations levels were not related to the age of the workers. Continued study of benzene-exposed workers (as well as industrial populations exposed to any clastogenic agent) with medical cytogenetic surveillance, environmental monitoring, and lifetime epidemiologic investigation is recommended.     

Leukemia risk in caprolactam workers exposed to benzene

PURPOSE: To investigate the leukemia risk in a group of benzene exposed workers. METHODS: We conducted a retrospective cohort mortality study on 311 men who worked between January 1, 1951 and December 31, 1968 in a Caprolactam plant in the Netherlands. In the production of Caprolactam (the Nylon 6 monomer) pure benzene is used as an extracting agent and the workers at this plant have been exposed to substantial concentrations of benzene. The cohort was followed for mortality until January 1, 2001. The total mortality was below the expected number, which was mainly caused by a deficit of cardiovascular disease mortality. RESULTS: In the total group, there was one death from leukemia, compared with an expected number of 1.17. Despite the substantial exposures to benzene (on average 159 ppm-years per person) there was no indication for increased leukemia mortality within the cohort. We have applied earlier quantitative risk assessments to our cohort and conclude that some of these assessments overestimate the risk observed in our cohort of Caprolactam workers.     

An improved method for the determination of phenol in the urine of workers exposed to benzene or phenol

Summary Interlaboratory comparison of phenol in urine analyses shows large variability, much larger than is normally associated with gas chromatographic analysis which suggest sample preparation problems are to blame. This paper describes a simple method of analysis which has been in use for four years in our laboratory. 2-Ethyl phenol is added to the urine as an internal standard; the sample is distilled and the distillate directly analysed by gas chromatography on a column packed with Tenax-GC using FID detectors. The detection limit is 0.1 mg/l and the coefficient of variation at 5.9 mg/l is 4.1 % (n = 8).     

Occupational medicine monitoring of workers exposed to benzene

Based on the present level of perception of the benzene biotransformation, the influence of reactive metabolites on the haematopoetic system - maintaining low MAK rates of 5 mg/m3 and below them - is presented. Consequences for the rate of the biological exposition test utilized at present result from this statement. The importance of a regular SCE determination in circulating lymphocytes, of the longtermed examination of possible damages of sperm and the differentiated analysis of individual kinds of lymphocytes, incl. of the cell-mediating immunity is emphasized besides the performance of a regular supervision of the external exposition, i.e. by means of personal dosimeters. To clarify the benzene influence, the research should be orientated on the damages of the cytoskeleton and the stroma cells within the haematopoetic system.     

苯系化合物作业工人心电图分析

目的：了解苯系物对心血管系统的危害程度。方法：1998年8月对我市某造漆接毒作业工人115名及不接毒作业人员110名（对照组）,进行心电图检查。结果：苯系物使作业工人神经系统、血液系统受到损害,因而也间接地使心血管系统受到损害。     

接触苯系物对作业人员血象影响的研究

[目的]分析苯系物作业工人血象特征,了解苯系物对作业工人血液系统的危害现状。[方法]使用东亚Xi-1800全自动血细胞分析仪进行血常规检测,比较接触组(接触苯系物)和对照组(非接触苯系物)白细胞、中性粒细胞绝对值、红细胞、血红蛋白和血小板均值以及异常检出率的差异。[结果]苯系物作业工人外周血中性粒细胞绝对值(P<0.01)平均水平较对照组低;白细胞减少、中性粒细胞绝对值偏低检出率高于对照组(P<0.05)。[结论]接触苯系物对人体外周血白细胞、中性粒细胞绝对值等有一定的影响。     

Biological monitoring of workers exposed to benzene in the coke oven industry.

Workers in the coke oven industry are potentially exposed to low concentrations of benzene. There is a need to establish a well validated biological monitoring procedure for low level benzene exposure. The use of breath and blood benzene and urinary phenol has been explored in conjunction with personal monitoring data. At exposures of about 1 ppm benzene, urinary phenol is of no value as an indicator of uptake/exposure. Benzene in blood was measured by head space gas chromatography but the concentrations were only just above the detection limit. The determination of breath benzene collected before the next shift is non-specific in the case of smokers. The most useful monitor at low concentrations appears to be breath benzene measured at the end-of-shift.     

Analysis of chromosomal aberrations in workers exposed to low level benzene.

Metaphase chromosome preparations were analysed as part of a larger study from a population occupationally exposed to benzene and compared with a control group. Forty eight of the 66 exposed individuals and 29 of the 33 controls had samples in which metaphase spreads could be evaluated. The incidence of chromosomal aberrations (particularly chromatid deletions and gaps) in the exposed group were slightly increased compared with the control group. This increase was of borderline significance in parametric statistical tests but was significant using Fisher's exact test. No lifestyle factors had any consistent effect on the incidence of chromosome aberrations, although there was a small reduction in gaps with increasing cigarette smoking. Older individuals had a higher incidence of chromosome exchanges and "other" aberrations. Individuals who reported a recent viral illness had a higher incidence of aberrations particularly gaps. There was no evidence of any correlation in the incidence of chromosome aberrations with any of the other biological parameters previously reported. The increased incidence of aberrations seen in the group exposed to benzene may result from a history of exposure to benzene. Nevertheless, other explanations such as sampling, interindividual variability, and unintentional bias in the selection of two groups cannot be excluded.     

An update of mortality among chemical workers exposed to benzene.

Mortality was updated to the end of 1982 for 594 employees exposed to benzene who had been studied previously and for an additional 362 exposed workers not studied previously. Cause specific mortality comparisons were made using United States white male, age, and calendar year adjusted rates. Total mortality was observed to have been significantly below expectation, and this was particularly evident for deaths from accidental causes. Mortality from skin cancer was significantly raised, although there were no unusual or common characteristics among the affected individuals which would suggest a link with exposure to benzene. A non-significant excess of total deaths from leukaemia was noted based on four observed cases; however, all four were myelogenous leukaemias and this represented a significant excess in that subcategory. These and other deaths of possible interest are reviewed in detail. Analyses by work area, duration of exposure, and cumulative dose index did not show patterns suggestive of a causal association between exposure to benzene and any particular cause of death.     

Hematotoxocity among Chinese workers heavily exposed to benzene

Benzene is a well-established hematotoxin. However, reports of its effects on specific blood cells have been somewhat inconsistent and the relative toxicity of benzene metabolites on peripheral blood cells in humans has not been evaluated. We compared hematologic outcomes in a cross-sectional study of 44 workers heavily exposed to benzene (median: 31 parts permillion [ppm] as an 8-hr time-weighted average [TWA] and 44 age and gender-matched unexposed controls from Shanghai, China. All hematologic parameters (total white blood cells [WBC], absolute lymphocyte count, platelets, red blood cells, and hematocrit) were decreased among exposed workers compared to controls, with the exception of the red blood cell mean corpuscular volume (MCV), which has higher among exposed subjects. In a subgroup of workers who were not exposed to more than 31 ppm benzene on any of 5 sampling days (n = 11, median 8 hr TWA = 7.6 ppm, range = 1–20 ppm), only the absolute lymphocyte count was significantly different between exposed workers (mean [sd] 1.6 [0.4] x 10³ μL) and controls (1.9 [0.4] x 10³ μL, p = 0.03). Among exposed subjects, a dose-response relationship with various measures of current benzene exposure (i.e., personal air monitoring, benzene metabolites in urine) was present only for the total WBC count, the absolute lymphocyte count, and the MCV. Correlations between benzene metabolites and hematologic parameters were generally similar, although hydroquinone was somewhat more strongly associated with a decrease in the absolute lymphocyte count, and catechol was more strongly associated with an increase in MCV. Morphologic review of peripheral blood slides demonstrated an excess of red blood cell abnormalities (i.e., stomatocytes and target cells) only in the most heavily exposed workers, with no differences in granulocyte, lymphocyte, or platelet morphology noted. Although benzene can affect all the major peripheral blood elements, our results support the use of the absolute lymphocyte count as the most sensitive indicator of benzene-induced hematotoxicity. © 1995 Wiley-Liss, Inc.     

某县接苯作业工人职业健康检查情况分析

目的探讨某县辖区内苯作业工人职业健康检查结果与行业、工龄及其他因素的关系,以进一步保障苯作业工人的健康权益。方法收集苯作业工人的职业健康检查和治疗情况,按行业、作业工龄和治疗情况进行分析。结果某县辖区内苯作业工人全部参加职业健康体检,箱包皮革行业苯作业工人职业健康复查率最高,苯作业工人工龄大于2年的复查率高,但是复查对象经及时治疗后恢复情况好。结论职业健康检查能及时发现苯对工人健康的早期损害或可疑对象,定期体检有利于早诊断、早治疗、早康复。     

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。