Monitoring of arsenic exposure with speciated urinary inorganic arsenic metabolites for ion implanter maintenance engineers

For wafer fabrication in the semiconductor industry, maintenance engineers are potentially exposed to hazards during their work of disassembling machine components for cleanup. One special concern is the presence of arsenic or arsenic compounds in the working environment. This study analyzed speciated urinary inorganic arsenic metabolites of the maintenance engineers using high-performance liquid chromatography-hydride generation atomic absorption spectrometry to study the potential arsenic exposure during their maintenance work. In total, from six wafer fabrication facilities, 30 maintenance engineers were recruited as the exposed group and another 12 office-based engineers served as the control group. First morning-voided urine samples of each study subject were collected for 7 consecutive days. The levels of total urinary inorganic arsenic metabolites for the exposed group were 1.7+/-1.4, 1.4+/-1.1, 6.2+/-6.7, 20.2+/-14.1, and 29.5+/-17.2 micro g/L for As3+, As5+, monomethylarsonic acid, dimethylarsinic acid, and total inorganic arsenic, respectively. Both the concentration of monomethylarsonic acid and its percentage in total urinary inorganic arsenic metabolites showed significantly ascending trends for the control group, for the engineers without preventative maintenance work prior to their urine sampling, and for the engineers with such work prior to their urine sampling (P<0.05 and P<0.0005, respectively). The data also suggested that, at low-level occupational arsenic exposure, the concentration of total urinary inorganic arsenic metabolites might be misleading due to the confounding effect resulting from intake of seafood, such as arsenosuger. Nevertheless, monitoring of urinary arsenic species by using the percentage change of monomethylarsonic acid in total urinary inorganic arsenic metabolites as an indicator for the verification of arsenic exposure is helpful and appropriate in such cases.     

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.     

Relation between airborne arsenic trioxide and urinary excretion of inorganic arsenic and its methylated metabolites.

The relation between exposure to As2O3 fumes and dust, and the urinary excretion of inorganic arsenic metabolites (monomethylarsonic acid, dimethylarsinic acid, unchanged inorganic arsenic) has been studied in 18 workers from a sulphuric acid producing plant. The concentration of arsenic in the breathing zone of each worker was measured during five consecutive days and urine samples were obtained after one shift and before the next. The collection efficiency of the air sampling system exceeded 95%. The time weighted average exposure (TWA) concentrations of As2O3 ranged from 6 to 502 micrograms As/m3 and were log normally distributed. Although exposure probably occurred by ingestion as well as inhalation, statistically significant correlations (log scales) were found between airborne TWA of As2O3 and the inorganic arsenic metabolites in urine collected immediately after the shift, or just before the next shift. For a TWA of 50 micrograms As/m3, the mean concentration of the sum of the three inorganic arsenic metabolites in a postshift urine sample amounted to about 55 micrograms arsenic/g creatinine (95% confidence interval (95% CI) 47-62). Higher estimates of urinary arsenic reported by other authors are probably due either to the influence of dietary organoarsenicals when total arsenic is measured in urine or to a low retention efficiency of the air sampling system for As2O3 in the vapour phase.     

Relation between airborne arsenic trioxide and urinary excretion of inorganic arsenic and its methylated metabolites.

The relation between exposure to As2O3 fumes and dust, and the urinary excretion of inorganic arsenic metabolites (monomethylarsonic acid, dimethylarsinic acid, unchanged inorganic arsenic) has been studied in 18 workers from a sulphuric acid producing plant. The concentration of arsenic in the breathing zone of each worker was measured during five consecutive days and urine samples were obtained after one shift and before the next. The collection efficiency of the air sampling system exceeded 95%. The time weighted average exposure (TWA) concentrations of As2O3 ranged from 6 to 502 micrograms As/m3 and were log normally distributed. Although exposure probably occurred by ingestion as well as inhalation, statistically significant correlations (log scales) were found between airborne TWA of As2O3 and the inorganic arsenic metabolites in urine collected immediately after the shift, or just before the next shift. For a TWA of 50 micrograms As/m3, the mean concentration of the sum of the three inorganic arsenic metabolites in a postshift urine sample amounted to about 55 micrograms arsenic/g creatinine (95% confidence interval (95% CI) 47-62). Higher estimates of urinary arsenic reported by other authors are probably due either to the influence of dietary organoarsenicals when total arsenic is measured in urine or to a low retention efficiency of the air sampling system for As2O3 in the vapour phase.     

Mutagenicity of urinary metabolites of benzidine and benzidine-based azo dyes

Summary The mutagenicity of urinary metabolites of benzidine and benzidine-based azo dyes was studied by using urine samples. The azo dyes studied were Direct Deep Black EX and Congo Red, both containing a 4,4′-diazobiphenyl group. After benzidine and the azo dyes had been administered orally to rats, urine was collected and extracted with ether. Mutagenicity of the urine extracts was tested in the Salmonella/mammalian-microsome assay. The results of the mutagenicity assay and the GC analysis of the urine extracts suggested that the azo dyes might decompose and release benzidine in the intestine of the rats. It was found that the urinary metabolites of benzidine, both N-acetylbenzidine, and N,N′-diacetylbenzidine, show stronger mutagenicity than benzidine itself. It was also found that the urine extracts from four men who had undergone “gastroscopy with Congo Red” were mutagenic.     

Risk factors for increased urinary inorganic arsenic concentrations from low arsenic concentrations in drinking water

A large number of drinking water supplies worldwide have greater than 50 microg l(- 1) inorganic arsenic in drinking water, and there is increasing pressure to reduce concentrations. Few studies have specifically considered low concentrations of arsenic in water supplies and the significance of other factors which may contribute to increased exposure. This study aimed to investigate risk factors for increased urinary inorganic arsenic concentrations, in a population exposed to 10 - 100 microg l(- 1) of arsenic in drinking water, as well as a control population with lower arsenic concentrations in their drinking water. Inorganic arsenic in urine was used as the measure of exposure. The median drinking water arsenic concentration in the exposed population was 43.8 microg l(- 1) (16.0 - 73 microg l(- 1)) and less than the analytical limit of detection of 1 microg l(- 1) (相似文献   

Airborne arsenic and urinary excretion of arsenic metabolites during boiler cleaning operations in a Slovak coal-fired power plant.

Little information is available on the relationship between occupational exposure to inorganic arsenic in coal fly ash and urinary excretion of arsenic metabolites. This study ws undertaken in a coal-fired power plant in Slovakia during a routine maintenance outage. Arsenic was measured in the breathing zone of workers during 5 consecutive workdays, and urine samples were obtained for analysis of arsenic metabolites--inorganic arsenic (Asi), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA)--prior to the start of each shift. Results from a small number of cascade impactor air samples indicated that approximately 90% of total particle mass and arsenic was present in particle size fractions >/= 3.5 micron. The 8-hr time-weighted average (TWA) mean arsenic air concentration was 48.3 microg/m3 (range 0.17-375.2) and the mean sum of urinary arsenic (SigmaAs) metabolites was 16.9 microg As/g creatinine (range 2.6-50.8). For an 8-hr TWA of 10 microg/m3 arsenic from coal fly ash, the predicted mean concentration of the SigmaAs urinary metabolites was 13.2 microg As/G creatinine [95% confidence interval (CI), 10.1-16.3). Comparisons with previously published studies of exposure to arsenic trioxide vapors and dusts in copper smelters suggest that bioavailability of arsenic from airborne coal fly ash (as indicated by urinary excretion) is about one-third that seen in smelters and similar settings. Arsenic compound characteristics, matrix composition, and particle size distribution probably play major roles in determining actual uptake of airborne arsenic.     

职业性砷暴露工人尿有机砷和8-羟基脱氧鸟苷水平的相关性

目的评价云南省某砒霜厂工人体内砷的代谢转化与DNA氧化损伤关系。方法选择云南省某砒霜厂一线工人37例（高暴露组）、管理和后勤人员16例（低暴露组）和当地近期无毒物接触史人员28例（对照组）为研究对象,检测尿中有机砷和8-羟基脱氧鸟苷水平,评价砷的代谢转化和DNA氧化损伤相关性。结果高、低暴露组男性尿有机砷分别为（0、48±0．37）mg／L、（0．08±0．05）mg／L,高、低暴露组女性尿有机砷分别为0．11mg／L、（0．30±0．24）mg／L,对照组均低于检出值下限（0．02mg／L）;高、低暴露组和对照组男性尿8-羟基脱氧鸟苷分别为（18．07±11．68）μmol／mol肌酐、（11．79±8．25）μmol／mol肌酐和（10．07±3．04）μmol／mol肌酐,高暴露组高于对照组（P〈0．05）;高、低暴露组和对照组女性尿8-羟基脱氧鸟苷浓度分别为84．35μmol／mol肌酐、（21．27±5．89）μmol／mol肌酐和（14．43±2．58）μmol／mol肌酐,暴露组女性尿8-羟基脱氧鸟苷浓度高于暴露组男性（P〈0．05）。尿中8-羟基脱氧鸟苷浓度随尿中有机砷浓度升高有上升趋势（rs=0．279,P=0．019）。结论砷职业暴露人群存在明显的DNA氧化损伤,对女性损伤更为明显,砷的代谢转化差异可能起关键作用。     

Distribution of urinary selenium and arsenic among pregnant women exposed to arsenic in drinking water

Inorganic arsenic (In-As) is a well-known toxicant and carcinogen found naturally in surface and groundwater around the world. Exposure can cause skin lesions, adverse reproductive outcomes, and cancer. There are two main pathways of arsenic (As) metabolism in humans: the reduction reactions, and the oxidative methylation reactions, where methyl groups are attached to As compounds to form monomethylarsenate (MMA) and dimethylarsenate (DMA). MMA, DMA, and In-As are excreted in urine. Urinary levels of another metalloid, selenium (Se), have recently been shown to be associated with increased As excretion and altered metabolite distribution. This study investigates this association, using data collected in a larger prospective study of arsenic and reproductive effects in Chile. This analysis included 93 pregnant women from Antofagasta. Data on demographic, behavioral, and other characteristics were obtained via interviews conducted by trained midwives, and spot urine samples were analyzed for As and Se concentration using inductively coupled plasma-mass spectrometry (ICP-MS). Urinary Se levels were found to be correlated with urinary As levels in bivariate analysis (r = 0.68, P < 0.01). Multiple linear regression analyses revealed that higher urinary Se levels were associated with increased urinary As excretion, increased %DMA, and decreased %In-As. The results of this study suggest that in populations exposed to arsenic, Se intake may be correlated with urinary As excretion, and may alter As methylation.     

Uptake and urinary excretion of aluminum among welders

Summary The urinary excretion of aluminum was measured in 23 welders before and after an exposure-free interval of 16 to 37 days. In addition, the concentration of aluminum in the air was measured at the work site of 16 aluminum welders on the same work-day as the first urine sample was taken. The concentration of aluminum in the urine depended on both the level and duration of exposure. The postshift urinary concentration of aluminum prior to an exposure-free interval was mainly related to the current air concentration, whereas the urinary concentration of aluminum determined after the exposure-free interval was related to total exposure duration (years). Among welders exposed for less than 1 year, the halftime for urinary concentration was about 9 days whereas welders exposed for more than 10 years had half-times calculated to be 6 months or longer. The results indicate that aluminum is retained and stored in at least two functional compartments of the body and is eliminated from these compartments at different rates.     

Histological types of lung cancer among smelter workers exposed to arsenic

The histological distribution of lung cancer was investigated in 93 men who had worked at a Swedish smelter with high levels of arsenic. A comparison was made with a group of 136 patients with lung cancer from the county where the smelter was located. Company records provided information on occupational exposure and data on smoking habits were obtained from a next of kin of each subject. No pronounced differences in the histological types of lung carcinomas between smelter workers and the reference group could be seen for smokers. Some analyses indicated an increased proportion of adenocarcinomas among the smelter workers, which confirmed earlier data, but these findings were difficult to interpret. Cases among smelter workers who had never smoked showed a histological distribution resembling that in smokers, indicating that the work environment at the smelter and smoking had a similar influence on the risk for different types of lung cancer.     

冶炼厂工人p15基因表达与砷及其代谢产物的关系

目的　探究小儿急性细菌性痢疾的病原菌分布特征并对其耐药情况进行分析，为小儿急性细菌性痢疾的治疗提供参考依据。方法　选取2016年1月—2019年7月亳州市人民医院确诊为小儿急性细菌性痢疾的80例患儿作为研究对象，对其临床资料如体温、腹泻次数、粪便状态等及实验检查如粪便病原菌培养和药物敏感试验结果进行统计分析。结果　小儿急性细菌性痢疾病原菌以福氏志贺菌（S. flexneri）检出率最高、宋内氏志贺菌（S. sonnei）其次、鲍氏志贺菌（S. boydii）最低；3群志贺菌同时耐药的抗生素有11种，耐药率较高的抗生素有氨苄西林、氨苄西林舒巴坦、环丙沙星、庆大霉素；敏感率较高的有厄他培南、亚胺培南、哌拉西林他唑巴坦、头孢他啶；3群志贺菌对哌拉西林他唑巴坦敏感率均为100%；各群志贺菌耐药情况在各年度大致相同，氨苄西林舒巴坦、庆大霉素与妥布霉素耐药例数逐年递增，S. sonnei和S. boydii耐药抗生素相对S. flexneri较少。结论　小儿急性细菌性痢疾病原菌耐药情况不容乐观，要加强对小儿急性细菌性痢疾的病原菌培养及耐药监测，合理使用抗生素，控制病原菌耐药演变与流行。     

Assessment of exposure to arsenic among smelter workers: A five-year follow-up

In a group of 43 smelter workers exposed to inorganic arsenic dust for 13-45 years, nerve conduction velocities (NCVs) were significantly lower in two peripheral nerves as compared with matching referents. With multivariate data analysis, a significant negative correlation was found between cumulative absorption of arsenic and NCV in four examined nerves and the sural amplitude. Clinical symptoms of neuropathy and other symptoms related to arsenic exposure were moderate, though the difference between the groups was significant. The mean total absorption of arsenic was calculated to be less than 5 g, and the maximal absorption about 20 g. These data indicate that the adverse effect of arsenic on the peripheral nerves is dependent on long-term exposure rather than on short-term fluctuations in exposure levels. © 1994 Wiley-Liss, Inc.     

Histological types of lung cancer among smelter workers exposed to arsenic.

The histological distribution of lung cancer was investigated in 93 men who had worked at a Swedish smelter with high levels of arsenic. A comparison was made with a group of 136 patients with lung cancer from the county where the smelter was located. Company records provided information on occupational exposure and data on smoking habits were obtained from a next of kin of each subject. No pronounced differences in the histological types of lung carcinomas between smelter workers and the reference group could be seen for smokers. Some analyses indicated an increased proportion of adenocarcinomas among the smelter workers, which confirmed earlier data, but these findings were difficult to interpret. Cases among smelter workers who had never smoked showed a histological distribution resembling that in smokers, indicating that the work environment at the smelter and smoking had a similar influence on the risk for different types of lung cancer.     

Cancer risk among workers at a copper/nickel smelter and nickel refinery in Finland

Summary A total of 1388 workers employed for at least 3 months at a copper/nickel smelter and nickel refinery were followed up for cancer from 1953 to 1987 through the Finnish Cancer Registry. There were 1339 male and 49 female workers, making a total of 27130 and 706 person-years, respectively. All of the women worked in the refinery, which opened in 1960, the same year the smelting of nickel began. A total of 67 cancers were diagnosed among the men, the standardized incidence ratio for all cancers being 1.0. No cancer was found among the women (1.8 expected). The risk of cancer among men was analysed according to primary site, exposure to nickel, type of work, years since first exposure and age at diagnosis. In the subcohort of nickel refinery workers, one case of sinonasal cancer was observed, against 0.02 expected, but otherwise no significantly increased risks of cancer were found. In addition to the small size of the cohort, the non-positive finding concerning lung cancer might be related to the relatively low arsenic exposure and, perhaps, to the late commencement of nickel production.     

Comparison of the urinary excretion of arsenic metabolites after a single oral dose of sodium arsenite,monomethylarsonate, or dimethylarsinate in man

Summary The urinary elimination of the metabolites of arsenic has been followed up as a function of time in volunteers who ingested a single oral dose of arsenic (500 g As) either as sodium arsenite (As_i), monomethylarsonate (MMA), or cacodylate (DMA). The excretion rate increased in the order As_i < DMA < MMA. After 4 days, the amount of arsenic excreted in urine represents 46, 78, and 75% of the ingested dose in the case of As_i, MMA and DMA, respectively. With regard to the in vivo biotransformations, it is concluded that DMA is excreted unchanged; MMA is slightly (13%) methylated into DMA while roughly 75% of the arsenic excreted after ingestion of As_i is methylated arsenic (about 1/3 as MMA and about 2/3 as DMA).This study was supported by a grant from the Commission of the European Communities     

A study of factors influencing urinary arsenic excretion in exposed workers

This study was designed to evaluate the influence of occupational and non-occupational factors on urinary arsenic excretion in workers exposed to iAs (inorganic arsenic) in the dismantlement of a factory which once produced fertilisers. We measured iAs and its methylated metabolites in 108 urinary samples of workers exposed to iAs in July 2006. A total of 13.9% of the samples showed levels higher than the Biological Exposure Index (BEI) of 35 μg/l (mean value 23.9 μg/l). After the improvement of working conditions, in August–October 2006 we collected urinary samples from each of the 108 workers enrolled. We also administrated a questionnaire, in order to investigate the influence of occupational and non-occupational factors on the urinary arsenic excretion. A significant difference was observed in relation with seafood consumption and age stratification. We have found a significant reduction of urinary arsenic excretion between the two phases of biological monitoring, probably due to appropriate hygiene work-related interventions.     

砷职业暴露员工尿中价态砷含量与健康相关因素的分析

目的通过职业砷暴露水平与尿中总砷（TAs）和尿价态砷含量的测定,初步分析体内砷代谢产物（价态砷）与健康相关生化指标之间的关联性。方法选择2家有色金属冶炼企业砷暴露作业工人（暴露组）137人,其中砷暴露锡冶炼组97人、铅冶炼组40人。对照组为无砷接触者42人。暴露组及对照组均进行健康监护及收集晨尿,行尿中TAs及尿价态砷含量测定,并检测作业场所空气中砷及其化学物浓度,进行尿中TAs、价态砷与健康相关因素之间的相关分析。结果两厂砷暴露工作环境空气中含TAs浓度（中位数）为0．30（0．01—1．35）mg／m3。其中铅冶炼厂砷浓度为0．46（0．01—1．03）mg／m3,锡冶炼厂砷浓度为0．26（0．06—1．35）mg／m3。暴露组的TAs、二甲苯呻酸监（DMA）含量与对照组比较,差异有统计学意义（P〈0．01）;暴露组TAs与DMA之间呈正相关（相关系数r=0．693,P〈0．01）;DMA与丙氨酸转氨酶、天冬氨酸转氨酶（ALT、AST）之间呈正相关关系（r=0．148,P〈0．05、r=0．268,P〈0．01）、与血常规RBC、HGB呈负相关（r=-0．165,P=0．038、r=-0．149,P=0．015）。结论砷暴露作业工人在无机砷较高浓度下作业,体内无机砷甲基化后主要的代谢产物为DMA与MMA,且价态砷特别是DMA与TAs、ALT、AST呈正相关、与RBC、HGB呈负相关,说明DMA对肝细胞、红细胞存在一定损害作用。     

砷暴露人群尿中7-甲基鸟苷与砷的相关性研究

目的探讨广西南丹地区环境砷暴露居民尿7-甲基鸟苷(7-MG)与尿砷的关系。方法于2014年3月应用多阶段分层抽样方法在南丹长老乡抽取122名6~65岁居民,应用电感耦合等离子体质谱法(ICP-MS)检测尿液中的砷含量,用ELISA法测定尿液中7-MG含量。通过广义线性模型分析砷暴露与尿7-MG的关系。结果长老乡儿童尿7-MG水平(G:10.90μg/g cr)高于成人(G:6.82μg/g cr)(P0.05);Spearman相关分析显示成人及儿童尿7-MG水平与土壤砷、饮水砷、蔬菜砷、粮食砷均无统计学关联(P0.05);调整年龄、性别、BMI及吸烟(或被动吸烟)后,广义线性回归分析显示儿童尿7-MG与尿砷呈正向关联(P0.01);成人尿7-MG主要受吸烟和性别影响,与尿砷无统计学关联。结论本次调查的广西南丹长老乡儿童尿7-MG水平可能是砷暴露的一种相对敏感指标。     

镉砷接触工人肾功能损伤研究

目的　探讨镉、砷对作业工人肾功能的联合作用。方法　以我国中南某厂镉、砷作业工人 114名为本研究的职业接触对象。以尿镉 (UCd)、尿砷 (UAs)作为接触标志物 ,尿 β2 微球蛋白(Uβ2 MG)、尿白蛋白 (UALB)、尿N 乙酰 β D 氨基葡萄糖苷酶 (UNAG)作为镉、砷致肾小管和肾小球损害的效应标志物。结果　UCd、UAs水平与Uβ2 MG、UALB、UNAG水平间均为正相关 ,具有明显的剂量-效应关系 (P <0 .0 5 ,P <0 .0 1)。结论　镉、砷对作业工人肾脏功能的联合作用主要表现为相加作用。