二甲基甲酰胺作业工人皮肤污染量研究

目的 建立二甲基甲酰胺(DMF)接触工人皮肤污染量的测定方法,并对DMF接触工人皮肤污染情况进行研究.方法 选择不同岗位的37名DMF接触工人,随机分成异丙醇组(16人)和去离子水组(21人),分别以异丙醇和去离子水为擦拭溶剂,采用气相色谱法测定DMF的皮肤污染量,同时测定工人班末尿中甲基甲酰胺(NMF)含量,并对皮肤污染总量与尿中NMF进行相关分析.结果 异丙醇组均能检测出DMF含量,去离子水组均未检出DMF,样品图谱中其他杂峰与DMF峰能完全分离,无干扰.湿法岗位工人皮肤污染总量最高[(2.844±1.31)mg],后处理岗位[(2.50±0.95)mg]和干法岗位[(1.95±0.61)mg]次之,后处理三版印刷、干法配料和湿法配料岗位工人经呼吸道累积接触剂量分别为351.3、201.3、135.2 mg.3个岗位空气中DMF平均浓度为60.2、89.6、156.4 mg/m3,皮肤DMF污染总量与尿中NMF无明显相关,差异无统计学意义(r=0.176,P>0.05).结论 异丙醇是测定DMF皮肤污染较有效的擦拭溶剂;当工作场所空气中DMF浓度高于职业接触限值时,DMF以呼吸道吸收为丰要途径,但其皮肤吸收也不容忽视.     

Biological monitoring of workers exposed to dimethylformamide in a textile polyurethane unit

Dimethylformamide (DMF) is a universal solvent noted for its solubility in both aqueous and lipid media. It is hepatotoxic, and there are concerns about its carcinogenicity. Our objective was to determine the correlation between air monitoring measurements and biological measurements of a suitable metabolite of DMF in a cohort of operatives in a polyurethane production unit. This was done with a view to assessing how much the inhalation route contributed to total DMF exposure, mainly for control purposes. We investigated the relationship between personal air sample measurements of DMF and biological measurements of N-methylformamide (NMF) in nine adult subjects, recruited across the shifts, with varying levels of exposure to DMF. Personal exposure monitoring was carried out with a low-flow-rate Model 222-4 SKC pump, while post-shift urine samples were obtained for further analysis. Operatives were asked to abstain from consuming alcohol for 24 h before the designated shift, as advised by the laboratory responsible for the analysis of urine samples. We found a very strong statistical association between air sample measurements of DMF and NMF in the urine of the sample population (R(2) = 0.95, P < 0.0001). This study suggests that airborne exposure contributes significantly to elevated levels of NMF and, therefore, indicates that efforts should be concentrated on engineering controls in reducing workplace DMF exposure.     

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     

Diazo-positive metabolites in urine from workers exposed to aromatic nitro-amino compounds

Summary The amount of diazo-positive compounds in urine from workers at a chemical plant producing pharmaceuticals and explosives was determined in samples collected after work and after a holiday. Forty-five persons working with aromatic nitro-amino compounds (ANA) showed a statistically significant (p < 0.01) increase in the exposed samples (1.21 ± 1.40 mmol/mol creatinine) compared to the unexposed samples (0.56 ± 0.31 mmol/mol creatinine). No increase in the level of diazo-positive metabolites was found in the 25 workers not exposed to ANA compounds. In a follow-up study, 32 trinitrotoluene (TNT) workers were divided into three exposure categories and seemed to show a dose-dependent increase in the level of urinary diazopositive metabolites. However, there was a considerable interindividual variation. The method seems suitable for the biological assessment of exposure to ANA compounds — at least on a group level. This may be valuable, especially in situations where significant dermal uptake is expected.     

Occupational exposure to hexahydrophthalic anhydride: air analysis,percutaneous absorption,and biological monitoring

Summary Urinary hexahydrophthalic acid (HHP acid) levels were determined in 20 workers occupationally exposed to hexahydrophthalic anhydride (HHPA) air levels of 11–220g/m³. The levels of HHP acid in urine increased rapidly during exposure and the decreases were also rapid after the end of exposure. The elimination half-time of HHP acid was 5h, which was significantly longer than in experimentally exposed volunteers, possibly indicating distribution to more than one compartment. There was a close correlation between time-weighted average levels of HHPA in air and creatinine-adjusted levels of HHP acid in urine collected during the last 4 h of exposure (r = 0.90), indicating that determination of urinary HHP acid levels is suitable as a method for biological monitoring of HHPA exposure. An air level of 100 g/m³ corresponded to a postshift urinary HHP acid level of ca. 900 nmol/mmol creatinine in subjects performing light work for 8h. Percutaneous absorption of HHPA was studied by application of HHPA in petrolatum to the back skin of three volunteers. The excreted amounts of HHP acid in urine, as a fraction of the totally applied amount of HHPA, were within intervals of 1.4%–4.5%, 0.2%–1.3%, and 0%–0.4% respectively, indicating that the contribution from percutaneous absorption is of minor importance in a method for biological monitoring.     

Biological monitoring of workers exposed to N,N-dimethylformamide in the synthetic fibre industry

Objectives: Monitoring of workplace air and biological monitoring of 23 workers exposed to N,N-dimethylformamide (DMF) in the polyacrylic fibre industry was carried out on 4 consecutive days. The main focus of the investigation was to study the relationship between external and internal exposure, the suitability of the metabolites of DMF for biological monitoring and their toxicokinetic behaviour in humans.Methods: Air samples were collected using personal air samplers. The limit of detection (LOD) for DMF using an analytical method recommended by the Deutsche Forschungsgemeinschaft (DFG) was 0.1 ppm. The urinary metabolites, N-hydroxymethyl-N-methylformamide (HMMF), N-methylformamide (NMF), and N-acetyl-S-(N-methylcarbamoyl)-cysteine (AMCC), were determined in one analytical run by gas chromatography with thermionic sensitive detection (GC/TSD). The total sum of HMMF and NMF was determined in the form of NMF. The LOD was 1.0 mg/l for NMF and 0.5 mg/l for AMCC. Results and conclusions: The external exposure to DMF vapour varied greatly depending on the workplace (median 1.74 ppm, range <0.1–159.77 ppm). Urinary NMF concentrations were highest in post-shift samples. They also covered a wide range (<1.0–108.7 mg/l). This variation was probably the result of different concentrations of DMF in the air at different workplaces, dermal absorption and differences in the protective measures implemented by each individual (gloves, gas masks etc.). The urinary NMF concentrations had decreased almost to zero by the beginning of the next shift. The median half-time for NMF was determined to be 5.1 h. The concentrations of AMCC in urine were determined to be in the range from <0.5 to 204.9 mg/l. Unlike the concentrations of NMF, the AMCC concentrations did not decrease during the intervals between the shifts. For the exposure situation investigated in our study, a steady state was found between the external exposure to DMF and the levels of AMCC excreted in urine about 2  days after the beginning of exposure. AMCC is therefore excreted more slowly than NMF. The half-time for AMCC is more than 16 h. Linear regression analysis for external exposure and urinary excretion of metabolites was carried out for a sub-group of 12 workers. External exposure to 10 ppm DMF in air (the current German MAK value) corresponds to an average NMF concentration of about 27.9 mg/l in post-shift urine from the same day and an average AMCC concentration of 69.2 mg/l in pre-shift urine from the following day. NMF in urine samples therefore represents an index of daily exposure to DMF, while AMCC represents an index of the average exposure over the preceding working days. AMCC is considered to be better suited for biomonitoring purposes because (1) it has a longer half-time than NMF and (2) its formation in humans is more closely related to DMF toxicity. Received: 25 June 1999 / Accepted: 2 October 1999     

二甲基甲酰胺接触工人健康状况调查

目的 探讨接触甲基甲酰胺接触(DMF)企业工人的中毒易发工作年限及对接触工人健康状况的影响。 方法 于2018年2至5月,选择江苏省内部分地区32家接触DMF企业的2 457工人作为调查对象,采用横断面开展对接触工人健康状况的调查,并对健康监护资料及工作场所职业病危害因素检测资料进行统计学分析。 结果 接触DMF男性工人肝功能、B超异常阳性率高于女性,60~69岁年龄段接触工人的肝功能异常率、血压异常率和B超异常率高于其他年龄段,差异有统计学意义(P<0.05);21~30年工龄段接触工人血压异常率最高(39.2%,20/51),11~20年工龄段接触工人肝功能异常率最高(44.3%,120/271),0~10年工龄段接触工人B超异常率最高(60.4%,20/51)。 结论 长期接触DMF会影响工人的肝功能和血压,且接触工龄的增加,对肝脏、心血管等器官的慢性损害程度也随之增加。     

Methylene dianiline : assessment of exposure and cancer morbidity in power generator workers

Summary The biaromatic amine 4,4'-methylene dianiline (MDA) is an animal carcinogen, possibly also carcinogenic to humans. In a cohort of 595 power generator workers potentially exposed to MDA in a curing agent of an epoxy system, the overall standardised cancer incidence ratio (SIR) among males (n = 550), however, was only 0.52 [95% confidence interval (CI) 0.16–1.21] based on five observed cases. One male urinary bladder cancer case was found in comparison to 0.6 expected (SIR 1.67; 95% CI 0.04–9.31). This case was identified in an unexposed subcohort. High levels of MDA metabolites were ascertained in the urine of currently exposed workers, probably following percutaneous absorption. Although no evidence of an increased overall or bladder cancer risk was detected, the limitations of the study in regard to the size of the cohort, age and cancer latency preclude a definite risk assessment. The dermal absorption of MDA has been highlighted.     

Biological monitoring of workers exposed to low levels of 2-butoxyethanol

Objectives: (1) To assess the value of urinary butoxyacetic acid (BAA) measurement for the monitoring of workers exposed to low concentration of 2-butoxyethanol (BE); (2) to evaluate the in vivo effect of low occupational BE exposure on the erythrocyte lineage; and (3) to test the possible influence of genetic polymorphism for cytochrome P450 2E1 (CYP 2E1) on urinary BAA excretion rate. Methods: Thirty-one male workers exposed to BE in a beverage package production plant were examined according to their external (BE) and internal (BAA) solvent exposure. The effect of this exposure on erythrocyte lineage [red blood cell numeration (RBC), hemoglobin (Hb), hematocrit (Htc), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), haptoglobin (Hp), reticulocyte numeration (Ret) and osmotic resistance (OR)], hepatic [aspartate aminotransferase (GOT), alanine aminotransferase (GPT)] and renal [plasmatic creatinine, urinary retinol binding protein (RBP)] parameters was also investigated. DNA purified from whole blood was used for CYP 2E1 genotyping. Results: Average airborne concentration of BE was 2.91 mg/m³ (0.59 ppm) with a standard deviation of 1.30 mg/m³ (0.27 ppm). There was a relatively good correlation between external and internal exposure estimated by measuring BAA in post-shift urine samples (average 10.4 mg/g creatinine; r=0.55;P=0.0012). Compared with a matched control group (n=21) exposed workers had a statistically significant decrease (3.3%;P=0.03) in Hct while MCHC was increased (2.1%;P=0.02). No significant difference was observed either in other erythroid parameters or in hepatic and renal biomarkers. One exposed individual exhibited a mutant allele with increased cytochrome P450 oxidative activity which coincided with a very low urinary BAA excretion. Conclusions: Single determination of BAA in post-shift urine samples can be used to assess exposure to low levels of BE. A slight but significant effect on erythroid parameters suggesting membrane damage was observed in exposed workers. The influence of the genetic polymorphism for CYP 2E1 deserves further investigation for the interpretation of urinary BAA measurements. Received: 6 December 1996 / Accepted: 21 February 1997     

接触二甲基甲酰胺工人经皮暴露干预措施效果评价

目的 探讨聚氨酯合成革工人DMF经皮暴露的干预效果.方法 对聚氨酯合成革企业在职业卫生调查的基础上,选择3个工种5个岗位的26名接触二甲基甲酰胺(DMF)工人为观察对象,采取加强个人防护、工程防护及健康促进等干预措施,观察6个月,对工作场所空气中DMF浓度、手部漂洗液中DMF和工人班末尿中甲基甲酰胺(NMF)含量采用气相色谱法进行测定,比较干预前后指标的变化.结果 干预前,空气中DMF平均TWA为(63.27±52.67)mg/m3合格率为26.9%(7/26),尿中NMF平均浓度为(2.07±0.32)mg/g肌酐,手部漂洗法液中DMF平均含量为(0.88±0.40)mg.干预后,工作场所空气中DMF平均TWA为(29.95±23.79)mg/m3,合格率为53.8%(14/26),工作场所空气中DMF浓度下降了52.7%,与干预前比较,差异有统计学意义(P<0.01);尿中NMF平均浓度为(1.70±0.29)mg/g肌酐,尿中NMF含量下降了17.9%,与干预前比较,差异有统计学意义(P<0.04);手部漂洗法液中DMF平均含量为(0.41±0.81)mg,下降了53.4%,与干预前比较,差异有统计学意义(P<0.05).结论 对于合成革工人DMF经皮暴露采取工程控制、个体防护和健康促进的综合性干预措施,能达到有效控制的目的.

Abstract：

Objective To assess the effects of interventions on synthetic leather workers exposed to N,N-dimethylformamide (DMF) by skin.Methods Twenty-six workers exposed to DMF were recruited.The level of DMF in ambient or handwash solution and N-methylformamide (NMF) in end-shift urine samples were detected before interventions and after interventions for six months.Results After interventions the levels of DMF in ambient reduced 52.7 % from (63.27±52.67) mg/m3 to (29.95±23.79) mg/m3.The levels of NMF in urine samples reduced 17.9% from (2.07±0.32) mg/g Cr to (1.70±0.29) mg/g Cr (P<0.01).The mean level of DMF in handwash solution reduced 53.4% from 0.88±0.40 mg to 0.41±0.81 mg.Conclusion This study showed that the multi-intervention measures (engineering control,personal protection and health promotion) should be used for the synthetic leather workers occupationally exposed to DMF.     

Biological monitoring and possible health effects in workers occupationally exposed to methyl methacrylate

Summary Monitoring by means of blood and urine analysis for methanol was successfully applied in 32 male workers who were exposed to methyl methacrylate (MMA) monomer at 6 ppm as a geometric mean and at 112 ppm as the maximum. Measurement of time-weighted average (TWA) intensity of the vapor exposure was successfully conducted with a diffusive sampler with activated carbon cloth as an adsorbent. Methanol concentrations in whole blood, serum, and urine samples were measured by headspace gas chromtography. The methanol concentrations in the three biological samples collected at the end of 8-h workshifts related linearly with the TWA MMA vapor concentrations, with correlation coefficients of 0.8–0.9. Quantitative evaluation of MMA in vapor and of methanol in urine suggests that only 1.5% of MMA inhaled will be excreted in urine as methanol. There were no significant clinical symptoms or abnormal hematological or serum biochemical findings at this exposure level, except that some workers complained throat irritation and frequent cough and sputa. The results indicate that biological monitoring by analysis for methanol is sensitive enough to detect MMA exposure at levels at which no serious health effects are to be expected.     

Relation of exposure to dimethylformamide vapor and the metabolite,methylformamide, in urine of workers

Summary Exposure of DMF (dimethylformamide) and urinary MF (methyl-formamide-metabolite of DMF) were measured in nine male workers handling surface-treating agents containing DMF for 5 consecutive days. The amount of urinary MF correlated well with the exposure to DMF. The measurement of urinary MF is therefore useful as an index of exposure to DMF.The rate constant for MF excretion was estimated as 0.16/h, while that calculated from Krivanek's data averaged 0.21/h. The MF excretion delay was correlated with the daily alcohol consumption.     

Biological monitoring of vehicle mechanics and other workers exposed to low concentrations of benzene

 It has been suggested that the threshold limit value (TLV) for the time-weighted average (TWA), of benzene be lowered because of its possible leukemogenic effect at low exposure concentrations. This requires the development of new methods of biological monitoring. In this cross-sectional study the diagnostic power of blood and breath benzene and of urinary phenol, catechol, hydroquinone, S-phenylmercapturic acid, and muconic acid were compared in a population of 410 male workers exposed to benzene in garages, in two coke plants, and in a by-product plant. Benzene exposure was assessed by personal air sampling (charcoal tube and passive dosimeter). In all, 95% of the workers were exposed to less than 0.5 ppm benzene. According to the multiple regression equation, the muconic acid and S-phenylmercapturic acid concentrations detected in nonsmokers exposed to 0.5 ppm benzene were 0.3 mg/g and 6 μg/g, respectively (range 0.2–0.6 mg/g and 1.2–8.5 μg/g, respectively). With muconic acid very few false-positive test results were found, and this determination remained reliable even around a cutoff level of 0.1 ppm benzene. Moreover, the diagnostic power of this test proved to be good even when diluted or concentrated urine samples were not excluded. S-Phenylmercapturic acid (S-PMA) also performed fairly well. Blood and breath benzene as well as urinary phenol (PH) and hydroquinone (HQ) were clearly less suitable biomarkers than muconic acid (MA). Catechol (CA) was not associated with occupational benzene exposure. According to the results of biological monitoring, the skin resorption of benzene from gasoline or other fuels seems negligible. Correlation, multiple regression, and likelihood ratios consistently showed that MA and S-PMA concentrations were fairly good indicators of benzene exposure in the 0.1- to 1-ppm range, even in a population comprising both smokers and nonsmokers. PH, HQ, CA, and blood and breath benzene were less suitable, if at all, in the same exposure range. Received: 31 July 1996/Accepted: 29 November 1996     

Biological monitoring of occupational exposure to di(2-ethylhexyl) phthalate: survey of workers exposed to plastisols

OBJECTIVE: The aim of this study was to perform a biological monitoring survey of workers exposed to di(2-ethylhexyl)phthalate (DEHP) in a factory using polyvinyl chloride plastisols and to contribute additional occupational data of exposure particularly sparse in the industrial sectors where this plasticizer is used. METHOD: Three urinary metabolites of DEHP, mono(2-ethylhexyl)phthalate (MEHP), mono(5-carboxy-2-ethylpentyl)phthalate (MCEPP) and 2-ethylhexanoic acid (2-EHA) were quantified in five workers using a plastisol (containing 33% of DEHP) and in five unexposed workers (controls), during 5 days with pre- and post-shift sampling. Analyses were performed by high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) with on-line extraction. RESULTS: Median concentrations of pre- and post-shift urinary samples in the exposed workers (n = 25) were 16.1 and 55.9 mug/l for MEHP, 37.6 and 103.7 mug/l for MCEPP and 46.3 and 72.1 mug/l for 2-EHA, respectively. In the controls (n = 19), the corresponding values were 12.0 and 10.4 mug/l for MEHP, 38.1 and 11.4 mug/l for MCEPP and 31.9 and 46.0 mug/l for 2-EHA, respectively. There is a significant increase (Mann-Whitney U-test, P < 0.05) of post-shift excretion in the exposed workers versus unexposed controls and in post-shift versus pre-shift concentrations only in the exposed workers. CONCLUSION: MEHP and MCEPP are shown to be suitable biomarkers to assess DEHP exposure while 2-EHA, less specific but classified in the category 3 of the European Union (EU) reproductive toxicants, is also an interesting biomarker. There is clear evidence of occupational exposure of workers in this factory.     

Estimation of the percutaneous absorption of styrene in an industrial situation

This field study was designed to compare the level of styrene absorbed percutaneously with that absorbed by inhalation in a real situation in the fiberglass-reinforced polyester industry. Methods: The study protocol consisted of comparisons of the patterns of urinary excretion of styrene metabolites by four groups of workers, all of whom performed the same task at the same time in the same workshop but wore the following different protective equipment: total protection with an insulating suit and mask, respiratory equipment only, percutaneous protection only, and no protection. Results: The urinary excretion level of the group with total protection did not significantly differ from that of the group with respiratory protection only. Conclusions: Precutaneous absorption is not a particularly important pathway for styrene absorption during stratification work in the polyester industry. Completely insulating personal protective equipment provides no greater level of protection than does a respirator at positive pressure alone. Received: 14 April 1998 / Accepted: 4 August 1998     

GSTT1及GSTM1和CYP2E1基因多态性与二甲基甲酰胺所致肝脏损害的关系

目的 探讨GSTT1、GSTM1和CYP2E1基因多态性与二甲基甲酰胺(DMF)作业人员肝脏损害的关系.方法 以某皮革厂69名肝功能异常的DMF作业人员为病例组,选取与病例组相似岗位、DMF接触水平相近而肝功能正常的125名工人为对照组,应用聚合酶链反应(PCR)、PCR-RFLP方法分别对GSIT1、GSTM1和CYP2E1 PstI位点基因进行分型.结果 病例组和对照组中GSTM1阳性和GSTM1阴性的分布频率分别为59.42%、38.40%和40.58%、61.60%,两组间分布的差异有统计学意义(P=0.005),携带GSTM1阳性基因型个体发生肝功能异常的风险是GSTM1阴性基因型个体的2.34倍(OR=2.34,95%CI:1.29～4.29).而GSTT1和CYP2E1 PstI位点不同基因型在病例组和对照组中没有明显差异.结论 携带GSTM1阳性基因型个体的DMF作业人员发生肝功能异常的风险性可能增加.     

Dinitrotoluene: An assessment of occupational absorption during the manufacture of blasting explosives

Summary Two biological monitoring studies were carried out among workers in an explosives factory who were exposed to technical grade dinitrotoluene (DNT). In the first study urine samples from 28 workers were analysed for the metabolite 2,4-dinitrobenzoic acid (2,4-DNBA). Metabolite concentrations in urine were extremely low or non-detectable, prior to starting work at the beginning of the working week, but post-shift urine samples contained a mean 2,4-DNBA level of 17 mg/1. There were wide variations in the concentrations excreted in urine by different workers and by individual workers on consecutive days. Atmospheric levels of DNT (determined by personal monitoring) were found to be well below the recommended limit and therefore could not account for the observed excretion of 2,4-DNBA. It is suggested that skin may be the major route of absorption of DNT during this process.A second study was carried out to investigate the kinetics of absorption and excretion of DNT. Intensive urine sampling was carried out on five individuals over a 2-day period with additional samples over the subsequent 2 non-working days. Analysis for 2,4-DNBA showed that uptake of DNT is rapid and that the highest levels were normally seen in the end-of-shift specimens. Urine samples were analysed for other known metabolites of DNT which have been found in animal studies and it was shown that 2,4-DNBA is the major known metabolite which is excreted in human urine. Unchanged DNT was detected in blood samples taken during a single workshift at levels up to 250 ng/ml.It is concluded that there is a measurable uptake of DNT by the group of workers studied. The measurement of 2,4 DNBA in end-of-shift urine samples is an appropriate way of assessing the effectiveness of measures taken to reduce the absorption of DNT.     

Biological monitoring of methylhexahydrophthalic anhydride by determination of methylhexahydrophthalic acid in urine and plasma from exposed workers

Objective: To investigate whether methylhexahydrophthalic acid (MHHP acid) in urine and plasma can be used as a biomarker for exposure to methylhexahydrophthalic anhydride (MHHPA). Methods: MHHPA in air was sampled by Amberlite XAD-2 and analysed by gas chromatography (GC) with flame ionisation detection. MHHP acid in urine and plasma was analysed by GC with mass spectrometric detection. Workers occupationally exposed to MHHPA were studied. Air levels of MHHPA were determined by personal sampling in the breathing zone. Urinary levels of MHHP acid, a metabolite of MHHPA, were determined in 27 workers. In eight workers all urine was collected at intervals during 24 h. Plasma levels of MHHP acid were determined in 20 workers. Results: The time-weighted average (TWA) air levels ranged from 5 to 60 μg MHHPA/m³ during 8-h work-shifts. The urinary levels of MHHP acid increased during exposure and decayed after the end of exposure with an estimated half-life of about 6 h. A correlation was found between the TWA air levels of MHHPA and creatinine-adjusted MHHP acid levels in urine collected during the last 4 h of exposure. A correlation was also seen between the TWA air levels of MHHPA and the plasma concentrations of MHHP acid. An exposure to 20 μg MHHPA/m³ corresponded to about 140 nmol MHHP acid/mmol creatinine and about 40 nmol MHHP acid/l plasma. Conclusion: The results indicate that MHHP acid in urine or plasma may be used for biological monitoring of the exposure to MHHPA. Received: 4 October 1996 / Accepted: 2 January 1997     

Ambient and biochemical effect monitoring of workers exposed to ethylene oxide

Objectives: Ethylene oxide is an alkylating agent known to be a directly acting mutagen and carcinogen. This study describes the relationship between workplace ambient air concentrations of ethylene oxide and the concentration of N-2-hydroxyethylvaline in the globin of exposed workers. Methods: During the sterilization of medical equipment, 12 workers were occupationally exposed to ethylene oxide. Personal and stationary ambient air measurements were carried out to monitor the external exposure. The determination of the protein adducts was based on the N-alkyl-Edman method, introducing a new commercially available dipeptide standard for calibration purposes. Results: Ethylene oxide concentrations ranging from 0.2 to 8.5 ppm were found in the workplace air. The adduct concentrations ranged from 5,219 to 32,738 pmol N-2-hydroxyethylvaline/g globin in the case of regularly exposed workers (n = 9) and from 518 to 3,321 pmol N-2-hydroxyethylvaline/g globin for three persons with occasional contact with ethylene oxide. Conclusions: The Deutsche Forschungsgemeinschaft established in 1993 a relationship between the ethylene oxide concentration in ambient air and the amount of N-2-hydroxyethylvaline in human globin. By extrapolation, constant exposure to 1 ppm ethylene oxide should yield approximately 4,000 pmol N-2-hydroxyethylvaline/g globin. The ambient air concentrations of ethylene oxide and the amount of N-2-hydroxyethylvaline determined within the present study confirm this extrapolation in practice. In addition, the determination of adducts based on the use of commercially available dipeptide standards for calibration purposes turned out to be an advantageous alternative to the commonly used protein standards. Received: 18 February 1997 / Accepted: 9 June 1997     

Exposure monitoring and health effect studies of workers occupationally exposed to cyclohexane vapor

Summary A survey was conducted in the second half of a working week on 33 women who either applied glue (with cyclohexane as an almost exclusive solvent component) or worked in the vicinity of glue application. Carbon cloth-equipped diffusive samplers were used for personal measurement of time-weighted average intensity of exposure to the solvent. The geometric mean and the highest cyclohexane concentration observed in air were 27 ppm and 274 ppm, respectively. Concentrations of cyclohexanol in urine samples and cyclohexane in whole blood and serum collected at the end of a shift showed significant correlations with the solvent exposure levels. Urinary cyclohexanone also correlated, but with a smaller correlation coefficient. The observation suggests that cyclohexanol in urine and cyclohexane in blood or serum collected at the end of a shift are useful indicators of occupational exposure to cyclohexane vapor. Quantitative estimation of balance at the end of the shift suggested that only a minute portion (< 1%) of cyclohexane absorbed is excreted in the urine as cyclohexanol, almost exclusively as a glucuronide. A survey of subjective symptoms revealed an increase in the prevalence of dimmed vision and unusual smell, but hematology and serum biochemistry testing did not indicate any specific signs.