Biological monitoring of occupational exposure to inorganic arsenic

OBJECTIVES: This study was undertaken to assess reliable biological indicators for monitoring the occupational exposure to inorganic arsenic (iAs), taking into account the possible confounding role of arsenicals present in food and of the element present in drinking water. METHODS: 51 Glass workers exposed to As trioxide were monitored by measuring dust in the breathing zone, with personal air samplers. Urine samples at the end of work shift were analysed for biological monitoring. A control group of 39 subjects not exposed to As, and eight volunteers who drank water containing about 45 micrograms/l iAs for a week were also considered. Plasma mass spectrometry (ICP-MS) was used for the analysis of total As in air and urine samples, whereas the urinary As species (trivalent, As3; pentavalent, As5; monomethyl arsonic acid, MMA; dimethyl arsinic acid, DMA; arsenobetaine, AsB) were measured by liquid chromatography coupled with plasma mass spectrometry (HPLC-MS) RESULTS: Environmental concentrations of As in air varied widely (mean 84 micrograms/m3, SD 61, median 40) and also the sum of urinary iAs MMA and DMA, varied among the groups of exposed subjects (mean 106 micrograms/l, SD 84, median 65). AsB was the most excreted species (34% of total As) followed by DMA (28%), MMA (26%), and As3 + As5 (12%). In the volunteers who drank As in the water the excretion of MMA and DMA increased (from a median of 0.5 to 5 micrograms/day for MMA and from 4 to 13 micrograms/day for DMA). The best correlations between As in air and its urinary species were found for total iAs and As3 + As5. CONCLUSIONS: To avoid the effect of As from sources other than occupation on urinary species of the element, in particular on DMA, it is proposed that urinary As3 + As5 may an indicator for monitoring the exposure to iAs. For concentrations of 10 micrograms/m3 the current environmental limit for iAs, the limit for urinary As3 + As5 was calculated to be around 5 micrograms/l, even if the wide variation of values needs critical evaluation and application of data. The choice of this indicator might be relevant also from a toxicological point of view. Trivalent arsenic is in fact the most active species and its measure in urine could be the best indicator of some critical effects of the element, such as cancer.

 

     

砷的职业接触生物监测指标

砷是一种自然界中多以化合物形式存在的常见类金属元素,在生产中应用广泛。随着职业接触人群越来越多,砷中毒越来越受到人们的重视。环境中的砷主要通过消化道、呼吸道和皮肤黏膜等进入人体,长期暴露于无机砷环境中可引起人体多种脏器损伤及其功能障碍,严重时可引发癌前病变。本文将对职业接触人群有关砷的生物监测指标予以综述。     

Biological monitoring of occupational exposure to methyl ethyl ketone in Japanese workers

The relationship between occupational exposure to methyl ethyl ketone (MEK) and its concentration in urine and blood was studied in a group of 72 workers in a printing factory. Personal exposure monitoring was carried out with passive samplers during the workshifts. The time weighted average (TWA) concentration of MEK ranged from 1.3 to 223.7 ppm, with a mean concentration of 47.6 ppm. In addition to MEK, toleuene, xylene, isopropyl alcohol, and ethyl acetate were detected as the main contaminants in all samples.At the end of the workshift, urine samples were collected to determine the urinary MEK, hippuric acid (HA), and creatinine, and blood samples were also collected at the same time for determination of MEK. The concentrations of urinary MEK ranged from 0.20 to 8.08 mg/L with a mean of 1.19 mg/L and significantly correlated with TWA concentrations of MEK in the air with a correlation coefficient of 0.889 for uncorrected urine samples. The concentration of MEK in the blood was also significantly correlated with the TWA concentration of MEK with a correlation coefficient of 0.820.From these relationships, MEK concentrations in urine and blood corresponding to the threshold limit value-TWA (200 ppm; ACGIH 1992) were calculated to be 5.1 mg/L and 3.8 mg/L as a biological exposure index (BEI), respectively. Although the BEI for urinary MEK obtained from the present study was higher than that of previous reports and ACGIH's recommendation (2.0 mg/L), the BEI agreed well with a previous study in Japan. On the other hand, the relationship between toluene exposure and urinary HA level, an index of toluene exposure, was also studied at the same time. The urinary concentration of HA corresponding to TWA at 100 ppm was 2.6 g/g creatinine as BEI. This value agreed well with both ACGIH's recommendation (2.5 g/g creatinine) and the values reported by Japanese researchers who have studied Japanese workers. Ethnic differences of MEK metabolism may affect the relationship between exposure and BEI.     

砒霜厂工人外周血淋巴细胞Dicer基因相对表达与尿砷代谢产物的关系研究

目的 通过比较职业性砷暴露人群与对照人群外周血淋巴细胞Dicer基因表达的差异,探讨职业性砷暴露人群外周血淋巴细胞中Dicer基因的表达与尿砷代谢产物之间的关系.方法 于2011年选取43名砒霜厂职业性砷暴露工人为暴露组,23名无砷暴露史人群为对照组,采用TRIzol法提取淋巴细胞中的总RNA,利用实时荧光定量PCR方法检测Dicer基因的表达,采用氢化物发生原子吸收分光光度法检测尿中各类砷化合物的含量.结果 砒霜厂工人无机砷、甲基胂酸、二甲基胂酸、总砷含量均高于对照组,二级甲基化指数低于对照组,外周血淋巴细胞中Dicer基因mRNA的表达(6.90±0.24)高于对照组(5.08±0.24),差异均有统计学意义(P＜0.01).尿中无机砷、甲基胂酸、二甲基胂酸、总砷与外周血淋巴细胞中Dicer基因mRNA表达呈正相关(P＜0.01);二级甲基化指数与Dicer基因mRNA表达呈负相关(r=-0.384,P＜0.05).结论 职业性砷暴露工人外周血淋巴细胞Dicer基因表达升高,可能与砷代谢甲基化过程有关.     

Biological and environmental monitoring of occupational exposure of pharmaceutical plant workers to methotrexate

Summary The exposure of 11 pharmaceutical plant workers to methotrexate (MTX) was studied. Personal air samples were taken during the different manufacturing processes: drug compounding, vial filling, and tablet preparation. The uptake of MTX was established by the determination of MTX in urine. MTX was analyzed using the fluorescence polarization immunoassay (FPIA), a method that is frequently used for monitoring serum levels in patients treated with MTX. The FPIA method was modified in such a way that MTX could be measured quickly and efficiently in air and urine samples. MTX was detected in air samples of all workers except for those involved in the vial filling process (range: 0.8–182 g/m³; median: 10 g/m³). The highest concentrations were observed for workers weighing MTX (118 and 182 g/m³). MTX was detected in urine samples of all workers. The mean cumulative MTX excretion over 72–96 h was 13.4 g MTX-equivalents (range: 6.1–24 g MTX-equiva g MTX-equivalents (range: 6.1–24 g MTX-equivalents). lents). A significantly lower background level of 10.2 g A significantly lower background level of 10.2 g MTX-equivalents was measured in urine of 30 control persons (range: 4.9–21 g MTX-equivalents).     

Biological monitoring of occupational exposure ton-hexane by measurement of urinary 2,5-hexanedione

Summary Occupational exposure ton-hexane in shoe factory workers was monitored by measuring urinary 2,5-hexanedione, the major metabolite of this solvent and the probable cause of peripheral neuropathy in exposed workers. Solvent pollution was monitored in the work environments of 189 employees, of whom 123 (65%) worked in Alicante, Spain, and 66 (35%) in Veneto, Italy. 2,5-Hexanedione was measured in spot urine samples collected from workers at the end of the shift. Information on working conditions was obtained from a previous study. A significant linear correlation was found between mean environmental concentration ofn-hexane and urinary concentration of 2,5-hexanedione. The variability in the correlation may have been due to the variable use of protective clothing (gloves), and to variations in exposure during the working week. In numerous workers, percutaneous absorption ofn-hexane represented as much as 50% of the total absorbed dose. Urinary concentrations of 2,5-hexanedione tended to increase during the working week. Simultaneous exposure ton-hexane and toluene tended to reduce urinary excretion of 2,5-hexanedione, whereas exposure ton-hexane and methyl ethyl ketone tended to increase excretion of the metabolite.     

职业性砷暴露对尿砷及外周血miRNA的影响

目的 探讨职业性砷暴露工人尿中不同化学形态砷含量及甲基化能力与外周血miRNA的关系。方法 采用自身对照，选取某矿山55名工人，问卷收集基本信息；采集研究对象正在接触时与脱离接触3个月后的尿液和外周血，高效液相色谱-电感耦合等离子质谱联用(HPLC-ICP-MS)法检测尿中三价及五价无机砷(inorganic arsenic, iAs³⁺、iAs⁵⁺)、一甲基砷酸(monomethylarsonic acid, MMA)、二甲基砷酸(dimethylarsinic acid, DMA)的含量；以尿中四种形态砷含量总和为总砷(total arsenic, tAs),并以一甲基化率(primary methylated index, PMI)、二甲基化率(secondary methylated index, SMI)为指标，计算甲基化能力；同时，采用实时荧光定量PCR检测外周血miR-155、miR-191、miR-200b相对表达量。结果 正在接触时工人尿中iAs³⁺、MMA、DMA、iAs⁵⁺、t...     

Assessment of occupational exposure to inorganic arsenic based on urinary concentrations and speciation of arsenic

An analytical speciation method, capable of separating inorganic arsenic (As (V), As (III] and its methylated metabolites (MMAA, DMAA) from common, inert, dietary organoarsenicals, was applied to the determination of arsenic in urine from a variety of workers occupationally exposed to inorganic arsenic compounds. Mean urinary arsenic (As (V) + As (III) + MMAA + DMAA) concentrations ranged from 4.4 micrograms/g creatinine for controls to less than 10 micrograms/g for those in the electronics industry, 47.9 micrograms/g for timber treatment workers applying arsenical wood preservatives, 79.4 micrograms/g for a group of glassworkers using arsenic trioxide, and 245 micrograms/g for chemical workers engaged in manufacturing and handling inorganic arsenicals. The maximum recorded concentration was 956 micrograms/g. For the most exposed groups, the ranges in the average urinary arsenic speciation pattern were 1-6% As (V), 11-14% As (III), 14-18% MMAA, and 63-70% DMAA. The highly raised urinary arsenic concentrations for the chemical workers, in particular, and some glassworkers are shown to correspond to possible atmospheric concentrations in the workplace and intakes in excess of, or close to, recommended and statutory limits and those associated with inorganic arsenic related diseases.     

Biological monitoring of occupational exposure to cyclohexane by urinary 1,2- and 1,4-cyclohexanediol determination

Objectives: This article reports the results obtained with the biological and environmental monitoring of occupational exposure to cyclohexane using 1,2-cyclohexanediol (1,2-DIOL) and 1,4-DIOL in urine. The kinetic profile of 1,2-DIOL in urine suggested by a physiologically based pharmacokinetic (PBPK) model was compared with the results obtained in workers. Methods: Individual exposure to cyclohexane was measured in 156 workers employed in shoe and leather factories. The biological monitoring of cyclohexane exposure was done by measurement of 1,2-DIOL and 1,4-DIOL in urine collected on different days of the working week. In all, 29 workers provided urine samples on Monday (before and after the work shift) and 47 workers provided biological samples on Thursday at the end of the shift and on Friday morning. Another 86 workers provided biological samples at the end of the work shift only on Monday or Thursday. Results: Individual exposure to cyclohexane ranged from 7 to 617 mg/m³ (geometric mean value 60 mg/m³). Urinary concentrations of 1,2-DIOL (geometric mean) were 3.1, 7.6, 13.2, and 6.3 mg/g creatinine on Monday (pre- and postshift), Thursday (postshift) and Friday (pre-shift), respectively. The corresponding values recorded for 1,4-DIOL were 2.8, 5.1, 7.8, and 3.7 mg/g creatinine. A fairly close, statistically significant correlation was found between environmental exposure to cyclohexane and postshift urinary 1,2-DIOL and 1,4-DIOL on Monday. Data collected on Thursday and Friday showed only a poor correlation to exposure with a wide scatter. Both metabolites have a urinary half-life of close to 18 h and accumulate during the working week. Conclusions: Comparison between data obtained from a PBPK model and those found in workers suggests that 1,2-DIOL and 1,4-DIOL are urinary metabolites suitable for the biological monitoring of industrial exposure to cyclohexane. Received: 17 June 1998 / Accepted: 23 September 1998     

Biological monitoring of environmental and occupational exposure to mercury

Summary Biological monitoring was used to assess mercury exposure from occupational and environmental sources in a group of chloralkali workers (n = 89) and in a control group (n = 75). In the control group, the median value for blood mercury (B-Hg) was 15 nmol/l, that for serum mercury (S-Hg) was 4 nmol/l and that for urinary mercury (U-Hg) was 1.1 nmol/mmol creatinine. Corresponding levels in the chloralkali group were 55 nmol/l, 45 nmol/l and 14.3 nmol/mmol creatinine, respectively. In the control group, there were statistically significant relationships between fish consumption and both B-Hg and S-Hg values (P < 0.001), whereas U-Hg correlated best with the individual amalgam burden (P < 0.01). In the chloralkali group, the mercury levels in blood and urine were significantly related to the type of work (P < 0.001) but not to the length of employment, to fish consumption or to the quantity of dental amalgam fillings. In both groups there were poor correlations between smoking or alcohol intake and the mercury levels in blood and urine. The results strongly suggest that fish is an important source of methylmercury exposure and that amalgam fillings are probably the most important source of inorganic mercury exposure among occupationally unexposed individuals. In the chloralkali group, mercury exposure from fish and amalgam was overshadowed by occupational exposure to inorganic mercury.     

Biological monitoring of occupational exposure to benzene and toluene

This study was carried out to evaluate the biological monitoring of occupational exposure to benzene and toluene in a total number of 31 male exposed workers and 30 control subjects. The present study showed a statistically significant higher level of biological indices of exposure (p < 0.01) of phenol and hippuric acid in urine of workers exposed to benzene and toluene than control subjects. Significant changes (p < 0.05, 0.01) in the levels of hematological and biochemical findings have been observed among exposed workers and control group. In addition, statistically significant higher levels of Mg, Mn and Ca were found among workers exposed to benzene and toluene while statistically significant lower levels of serum iron (p < 0.05) have been observed. No significant variations could be detected in the level of Zn and Cu between exposed and control subjects.     

Assessment of occupational exposure to inorganic arsenic based on urinary concentrations and speciation of arsenic.

An analytical speciation method, capable of separating inorganic arsenic (As (V), As (III] and its methylated metabolites (MMAA, DMAA) from common, inert, dietary organoarsenicals, was applied to the determination of arsenic in urine from a variety of workers occupationally exposed to inorganic arsenic compounds. Mean urinary arsenic (As (V) + As (III) + MMAA + DMAA) concentrations ranged from 4.4 micrograms/g creatinine for controls to less than 10 micrograms/g for those in the electronics industry, 47.9 micrograms/g for timber treatment workers applying arsenical wood preservatives, 79.4 micrograms/g for a group of glassworkers using arsenic trioxide, and 245 micrograms/g for chemical workers engaged in manufacturing and handling inorganic arsenicals. The maximum recorded concentration was 956 micrograms/g. For the most exposed groups, the ranges in the average urinary arsenic speciation pattern were 1-6% As (V), 11-14% As (III), 14-18% MMAA, and 63-70% DMAA. The highly raised urinary arsenic concentrations for the chemical workers, in particular, and some glassworkers are shown to correspond to possible atmospheric concentrations in the workplace and intakes in excess of, or close to, recommended and statutory limits and those associated with inorganic arsenic related diseases.     

Cancer and occupational exposure to arsenic: A study of pesticide workers

Mortality and morbidity experience was studied in 1,393 persons exposed to considerably high air concentrations of inorganic arsenicals for varying lengths of time during the manufacture and packaging of various pesticides in a plant in Baltimore, Maryland. Study subjects were traced for the period 1946–1977, and vital status was determined for 86.9% of 1,050 men and 66.8% of 343 women. The observed numbers of deaths from all and selected causes were compared with the expected numbers of deaths derived from population mortality rates. Among men, 23 deaths from lung cancer and 2 deaths from anemias represented statistically significant excesses over the expected numbers (P < 0.05). Lung cancer mortality was especially high in male production workers with presumed high exposure to arsenicals for a prolonged period of time. A dose-response effect was suggested for lung cancer mortality which increased with length of arsenical exposure, but no such relationship appeared for nonarsenical exposure. Workers with high arsenical exposure also had increased frequencies of such forms of arsenism as keratoses and perforation of the nasal septum. Analysis of the 23 male lung cancer deaths and 23 matched controls suggested a relationship, though not statistically significant, between lung cancer and antecedent keratoses. These findings provide strong evidence for a causal relationship between occupational exposure to inorganic arsenicals and lung cancer.     

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.     

Biological monitoring of arsenic exposure of gallium arsenide- and inorganic arsenic-exposed workers by determination of inorganic arsenic and its metabolites in urine and hair

In an attempt to establish a method for biological monitoring of inorganic arsenic exposure, the chemical species of arsenic were measured in the urine and hair of gallium arsenide (GaAs) plant and copper smelter workers. Determination of urinary inorganic arsenic concentration proved sensitive enough to monitor the low-level inorganic arsenic exposure of the GaAs plant workers. The urinary inorganic arsenic concentration in the copper smelter workers was far higher than that of a control group and was associated with high urinary concentrations of the inorganic arsenic metabolites, methylarsonic acid (MAA) and dimethylarsinic acid (DMAA). The results established a method for exposure level-dependent biological monitoring of inorganic arsenic exposure. Low-level exposures could be monitored only by determining urinary inorganic arsenic concentration. High-level exposures clearly produced an increased urinary inorganic arsenic concentration, with an increased sum of urinary concentrations of inorganic arsenic and its metabolites (inorganic arsenic + MAA + DMAA). The determination of urinary arsenobetaine proved to determine specifically the seafood-derived arsenic, allowing this arsenic to be distinguished clearly from the arsenic from occupational exposure. Monitoring arsenic exposure by determining the arsenic in the hair appeared to be of value only when used for environmental monitoring of arsenic contamination rather than for biological monitoring.     

Metabolic profile and assessment of occupational arsenic exposure in copper- and steel-smelting workers in China

Purpose  

Analyze the urine arsenic (As) metabolite profiles of workers in copper-and special steel-smelting plants and explore the potential occupationally As exposure as well as the individual arsenicosis risk.     

职业性农药接触对女工生殖功能的影响

目的 :探讨有机磷农药对女性生殖功能的影响。方法 :采用生殖流行病学调查方法 ,按照统一的妇女生殖健康调查表 ,以农药厂生产有机磷农药的一线女工 6 0 1名作为接触组 ,非农药厂的女工 873名作为对照组进行生殖功能状况调查比较。结果 :接触组女工早产 (8.2 0 %)、过期产 (7.6 4 %)、自然流产 (2 .83%)、新生儿出生低体重 (3.1 8%)、出生缺陷 (1 .0 6 1 %)和妊娠高血压综合症 (6 .4 1 %)的发生率均明显高于对照组 (χ2 =1 4 .71 2 ,8.96 6 ,8.0 70 ,4 .0 4 1 ,4 .384 ,4 .4 6 4 ;P =0 .0 0 0 ,0 .0 0 3,0 .0 0 4 ,0 .0 4 4 ,0 .0 36 ,0 .0 35 )。结论 :有机磷农药对女性的生殖功能有一定的影响 ,应提出相应的干预措施以保护女工的健康。     

Biological monitoring of pyrethroid exposure of pest control workers in Japan

Synthetic pyrethroids such as cypermethrin, deltamethrin and permethrin, which are usually used in pest control operations, are metabolized to 3-phenoxybenzoic acid (3-PBA) and excreted in urine. Though 3-PBA can be used to assess exposure to pyrethroids, there are few reports describing urinary 3-PBA levels in Japan. This study aimed to investigate the seasonal variation of the exposure levels of pyrethroids and the concentration of urinary 3-PBA among pest control operators (PCOs) in Japan. The study subjects were 78 and 66 PCOs who underwent a health examination in December 2004 and in August 2005, respectively. 3-PBA was determined using gas chromatography-mass spectrometry. The geometric mean concentration of urinary 3-PBA in winter (3.9 microg/g creatinine) was significantly lower than in summer (12.2 microg/g creatinine) (p<0.05). Geometric mean concentrations of urinary 3-PBA in the spraying workers and the not-spraying workers within 2 d before the survey were 5.4 microg/g creatinine and 0.9 microg/g creatinine for winter with a significant difference between the groups (p<0.05), and 12.3 microg/g creatinine and 8.7 microg/g creatinine for summer (p>0.05), respectively. A significant association of 3-PBA levels and pyrethroid spraying was thus observed only in winter. In conclusion, the results of the present study show that the exposure level of pyrethroids among PCOs in Japan assessed by monitoring urinary 3-PBA was higher than that reported in the UK but comparable to that in Germany. Further research should be accumulated to establish an occupational reference value in Japan.     

职业暴露和吸烟对焦炉工肺通气功能的影响

目的　研究职业暴露和吸烟对焦炉作业工人肺通气功能的影响。方法　对某焦化厂各炉炉顶、炉侧以及炉底进行环境有害物的监测;对2 34名焦炉作业工人进行吸烟指数的调查和肺通气功能测定。结果　焦炉作业环境有害物浓度呈炉顶>炉侧>炉底的趋势;吸烟的焦炉作业工人标化第一秒最大呼气量(FEV1,90 .8%±8.6 % )与第一秒最大呼气率(FEV1% ,95 .4 %±12 .4 % )均明显低于不吸烟组(10 0 .9%±14 .3%、10 8.9%±17.6 % ) ;吸烟的焦炉作业工人的标化最大肺活量(FVC)与职业接触苯溶物、苯并[a]芘和吸烟指数的偏相关系数分别为- 0 .2 4 9、- 0 .187和- 0 .36 8,FEV1与三者的偏相关系数分别为- 0 .2 5 5、- 0 .191和- 0 .388,FEV1%与三者的偏相关系数分别为- 0 .131、- 0 .10 7和- 0 .0 6 5 ;不吸烟的焦炉作业工人的FVC、FEV1和FEV1%与职业接触苯溶物的偏相关系数分别为- 0 .15 4、- 0 .0 5 2和- 0 .176 ,与苯并[a]芘的偏相关系数分别为- 0 .12 1、- 0 .0 37和- 0 .15 9。结论　焦炉作业工人肺通气功能与职业接触和吸烟指数均有一定的负相关。