Comparison between exhaled breath condensate analysis as a marker for cobalt and tungsten exposure and biomonitoring in workers of a hard metal alloy processing plant

Objective  Cobalt (Co), Tungsten (W) and Tungsten Carbides (WC) are major constituents of hard metal alloys. Whereas little is known about potential health hazards due to tungsten carbide exposure, occupational exposure to cobalt has been shown to induce a variety of respiratory diseases. Since the concentration of a potentially hazardous substance in the target organ is the most meaningful risk indicator in occupational medicine, the detection of hard metals in exhaled breath condensate (EBC) has been proposed to be a valuable instrument. The present study examines the correlation of Co and W concentrations in EBC and urine with one another and various spirometrical and clinical parameters to scrutinize this potential. Methods  A total of 62 subjects (90.3% males, age 40.6 ± 9.2 years) were recruited from a hard metal processing plant in Germany. Examinations included the airborne workplace exposure, a complete spirometry, measurements of Co and W concentrations in EBC and urine with high resolution inductive coupled plasma mass spectrometry (HR ICP-MS) and graphite furnace atomic absorption spectrometry (GFAAS). Results  Air concentrations ranged between 0.0019 mg/m3 and 0.074 mg/m3 for Co and 0.012 mg/m3 and 0.021 mg/m3 for W. Median urine concentrations and interquartile ranges of the exposed subjects ranged from 0.81 (0.0–1.46) μg/l for Co and 30.5 (14.5–57.7) μg/l for W. Median breath condensate metal concentrations and interquartile ranges ranged from 8.4 (5.0–13.9) μg/l for Co and 8.8 (4.4–18.5) μg/l for W. Urine concentrations of Co and W were closely related to the airborne workplace exposure that had been assessed by air monitoring. EBC concentrations of Co and W showed no correlations to urinary W and Co concentrations and the ambient monitoring results of the individual workplace, respectively. Cobalt EBC concentration was elevated in subjects who reported to have suffered from respiratory disease; both Co and W concentrations in EBC, however, decreased with increasing spirometrical signs of obstruction. Conclusion  According to our study, urinary concentrations of Co and W seem to be more reliable indicators of current workplace exposure than EBC concentrations. As far as new methods and exposure matrices for valid concentration measurements in respiratory organs and possible hazardous effects—especially of cobalt—in the lung are concerned, the present results are less clear-cut, and further research is required.     

Assessment of total exposure to phenol-formaldehyde resin glue in plywood manufacturing

Objective: Respiratory and dermal exposure to phenol-formaldehyde resin-glue components used in plywood manufacturing were assessed. Methods: Formaldehyde and phenol were monitored in the workplace air. Formaldehyde was measured both in the breathing zones of the workers and at stationary sampling sites. Phenol was used as a marker agent for dermal exposure due to its near-nonvolatility at the temperatures occurring during the present study and to its ready absorption through the skin, causing systemic exposure in addition to local skin rashes. Sampling and analytical methods were developed to measure the dermal exposure to phenol. Sampling was accomplished with whole-body dosimetry using Tyvek coveralls and cotton gloves. In addition, a liquid chromatography method was developed for the analysis of phenol from dermal exposure samples. Results: As expected, formaldehyde was noted to be the major compound causing respiratory exposure. When exposure assessment was done on the basis of air samples collected both at stationary sampling sites and in the breathing zones of the workers the agreement between the results obtained was good. The dermal sampling revealed that the workers were exposed to phenol, but the risk for toxic effects was slight due to the low concentrations of urinary phenol. Conclusions: We conclude that it is possible to use the stationary sampling method for the assessment of respiratory exposure in a plywood factory instead of the usually more complicated breathing-zone sampling. This study also demonstrates the importance of taking dermal exposure into account, at least due to the ability of the resins to cause skin rashes, in assessment of the exposure to chemicals in plywood manufacturing. Received: 8 December 1998 / Accepted: 25 March 1999     

父母职业接触铅对其子代某些形态和血液指标的影响

目的　评价铅对作业工人子代健康的影响。方法　选择父亲和 (或 )母亲从事铅作业的 14 7名城区儿童 ( 6～10岁 )为接触组 ,父母亲均不接触铅及其它化学毒物的儿童 99名为对照组。测定两组儿童身高、体重、胸围、发铅、血铅、血锌卟啉及智商和部分血液指标。结果　接触组发铅、血铅、血锌卟啉明显高于对照组 (P <0 0 1) ,血红蛋白、红细胞数明显低于对照组 (P <0 0 1) ,女性胸围发育明显落后于对照组 (P <0 0 1) ;上述改变以父亲母亲同时接触铅影响最大、父亲接触铅次之、母亲接触铅影响最小。结论　职业接触铅对子代健康有不良影响     

职业铅接触对男性工人腰椎骨折的影响

目的探讨职业铅接触对男性工人腰椎骨折的影响。方法以上海某蓄电池厂152名男性铅作业工人为研究人群。采用石墨炉原子吸收分光光度法测定血铅（aPb）、尿铅（UPb），应用单光子骨密度仪（SPA-4）测定工人骨蛮度，并做Z评分。拍摄腰椎侧位x线平片，并诊断有无腰椎骨折。结果铅作业工人血铅浓度0．85（0．33-1．90）μmol／L，尿铅浓度4．84（0．46-21．31）μg／g Cr，腰椎骨折发病率为19．7％。工人腰椎骨折发病率随年龄和工龄增长而升高，但差异无统计学意义（P〉0．05）。工人骨密度随血铅、尿铅水平升高而明显下降，差异有统计学意义（P〈0．05）。工人随着体内铅接触水平的升高，腰椎骨折发病率随之明显升高，差异有统计学意义（P〈05）并呈线性相关（r血铅=-0．977，P〈0．05；r尿铅=0．994，P〈0．01）。随着骨量减少，工人腰椎骨折发病率明显升高，差异有统计学意义（P〈0．01）并呈线性相关（r=-0．980，P〈0．01）。结论职业铅接触可能引起职业人群骨密度下降，腰椎骨折发病率增高，腰椎骨折的发生可能与骨量减少有关。     

职业铅接触对工人骨密度和骨代谢的影响

目的探讨职业铅接触对工人骨密度和骨代谢的影响。方法以上海某蓄电池厂298名铅作业工人为职业接触对象，同时选取该厂无职业铅接触史的办公室工作人员81名作为对照。血铅（BPb）、尿铅（UPb）为接触标志物；代表骨质疏松的Z评分、尿羟脯氨酸（HYP）、血清碱性磷酸酶（ALP）、血清骨碱性磷酸酶（BALP）、血清骨钙素（BGP）为效应标志物。应用单光子骨密度仪（SPA-4）测定工人骨密度。结果职业铅接触组人群BPb、UPb、HYP、ALP、BALP均高于对照组，其中男性差异有统计学意义（P〈0．01）；接触组BGP高于对照组，差异无统计学意义（P〉0．05）；接触组骨密度低于对照组，差异无统计学意义（P〉0．05）。与UPb 0-μg／gCr组比，各人群UPb10-μg／gCr组的骨密度均明显降低，差异有统计学意义（P〈0．01）；与BPb0～μg／L组比，男性BPb300-μg／L组的骨密度明显下降，差异有统计学意义（P〈0．01）。分别与UPb0-μg／gCr组、BPb0-μg／L组比，各人群UPb20-μg／gCr组、BPb300-μg／L组的HYP、ALP、BALP、BGP均明显升高，差异有统计学意义（P〈0．05）。随着体内铅接触水平的升高，人群骨质疏松的患病率和各骨代谢指标的异常率均随之明显升高，差异有统计学意义（P〈0．01），并呈线性相关（P〈0．01），但BGP的异常率与UPb无明显联系（P〉0．05）。计算得到基准剂量（BMD），推出基准剂量的95％低限水平（BMDL）。铅所引起的骨质疏松指标的BPb、UPbBMDL值均高于铅致骨代谢指标改变的BMDL值。结论职业铅接触能引起人群骨密度降低而导致骨质疏松，并且可以影响工人骨代谢。     

父母职业接触铅对其子女智力行为的影响

目的　评价铅对作业工人子女智力、神经行为的影响。方法　选择父亲和 (或 )母亲从事铅作业的 14 7名某市区儿童 (6～ 10岁 )为接触组 ,父母亲均不接触铅及其它化学毒物、居住在同一市区的儿童 99名为对照组。测定两组儿童血铅、发铅、血锌卟啉、智商和神经行为功能。结果　父母职业性接触铅其子女发铅、血铅、锌卟啉明显高于对照组 (P<0 0 1) ,血铅、发铅水平与智商水平基本呈负相关关系。行为功能简单反应时、数字跨度得分 ,接触组明显低于对照组(P <0 0 1) ;上述改变以父亲母亲同时接触铅影响最大、父亲接触铅次之、母亲接触铅影响最小。结论　父母职业接触铅增加其子女铅负荷 ,造成儿童的智力和神经行为不良影响     

Comparability of different methods of retrospective exposure assessment of metals in manufacturing industries

Many occupational case-control studies have relied on either self-report or exposure assessment based on job titles linked to a job exposure matrix (JEM) as opposed to the generally considered more accurate, but labor intensive, method of expert review of job histories. Our study examined the comparability of these different methods in assessing occupational exposure to the metals copper (Cu), lead (Pb), and iron (Fe) in manufacturing industries. Subjects were older people from a case-control study of a neurologic disease, and consisted of 188 individuals (72% male, 85% white) who had worked an average of 22.4 years in the manufacturing industry. An industrial hygienist review (IHR) of occupational history data from a comprehensive questionnaire was used as the reference method. The percent agreement (%A), sensitivity (SE), and specificity (SP) for direct self-report of metal exposures were: Cu, %A = 94.6, SE = 83.6, SP = 96.1; Pb, %A = 91.9, SE = 72.5, SP = 93.5; and Fe, %A = 82.7, SE = 64.5, SP = 88.1. Using the National Institute for Occupational Safety and Health (NIOSH) JEM, we analyzed the jobs of 115 of the 188 study subjects who had all their jobs listed in the JEM. Exposure assessment based on the NIOSH JEM compared with the IHR resulted in greater misclassification relative to direct self-report: Cu, %A = 81.5, SE = 21.2, SP = 89.2; Pb, %A = 86.0, SE = 0.0, SP = 92.6; and Fe, %A = 69.2, SE = 15.5, SP = 86.4. For all three study metals, combining the information from both direct self-report and the JEM did not improve upon the results compared with direct self-report alone. Due to the complex nature of metal exposure assessment, we suggest using an expert review of job histories whenever possible to minimize potential misclassification. Am. J. Ind. Med. 31:36–43 © 1997 Wiley-Liss, Inc.     

Application of classic epidemiological studies and proteomics in research of occupational and environmental exposure to lead,cadmium and arsenic

The metals/metaloids lead (Pb), cadmium (Cd), and arsenic (As) are among the leading toxic agents in the environment. They represent an important source of dangerous exposure in humans, particularly in industry workers. The most serious consequences of exposure to those heavy metals are cancers and cardiovascular diseases. In studies of human exposure to Pb, Cd, and As alone and in a mixture markers signaling the subtle, early lesions that occur in the human body are still lacking. It is appropriate to develop high throughput techniques and use non-invasive materials. The techniques currently used in classic epidemiological studies allow selection of single markers of changes of exposure to chronic low dose levels of metal/metaloids mixtures. However, application of proteomic techniques in such studies may allow the selection of new biomarkers of environmental and occupational exposure to heavy metals characterized by high sensitivity and specificity. As presented in our review paper, proteomic techniques in combination with appropriate statistical methods allow the selection of potential markers to estimate the changes in the human body when exposed to those heavy metals.     

Lead concentration in single hairs as a monitor of occupational lead exposure

Summary A rapid method for the analysis of 1-cm segments of single hairs has been developed. The hairs are washed with Freon TF in an ultrasonic bath and analyzed by electrothermal atomic absorption spectrometry. Due to diffusion of exogenous lead into the hairs the lead concentration increases along the hair shaft. Thus only the first 1-cm segment close to the hair root is used. In a reference population of 44 males no association was found between the hair lead concentration and age of the individual. Dark hairs tended to contain more lead than white hairs, but such difference was not apparent in occupationally exposed males. During four weeks blood and urine samples were collected from 87 males with occupational lead exposure, and hairs which had grown 1 cm during this period were then sampled and analyzed. The lead concentration in the first 1-cm segment of the hairs correlated significantly with the average lead concentration in blood and in urine, and -aminolevulinate in urine. Hair lead increases exponentially with increasing blood lead. A permissible limit of 60µg lead/100 ml blood corresponds to about 70µg lead/g hair or 3ng lead/cm hair. The analysis of single hairs for lead is recommended as a screening method.     

Effects of occupational exposure to polychlorinated biphenyls on urinary metabolites of neurotransmitters: A cross-sectional and longitudinal perspective

BackgroundPolychlorinated biphenyls (PCBs) are chemicals which were used for industrial purposes and are known to induce various adverse health effects. They are also known to be neurotoxic and numerous targets within the central nervous system have been identified in previous studies. Specifically, the neurotransmitters dopamine (DA) and norepinephrine (NE) are influenced by PCBs as indicated in studies involving animals. However, limited evidence has been published documenting PCB induced changes in the neurotransmitter system in humans.ObjectiveIn the present study, we examined the association between a higher PCB body burden following occupational exposure and possible changes in human neurotransmitter metabolites.MethodsWithin a medical surveillance programme called HELPcB (Health Effects in High-Level Exposure to PCB) that monitors adverse health effects of occupational PCB exposure, urine samples were obtained (n_T1 = 166; n_T2 = 177 and n_T3 = 141). The urinary concentrations of the metabolites homovanillic acid (HVA; for DA) and vanillylmandelic acid (VMA; for NE) were analyzed. Blood samples were obtained by vena puncture in order to determine the internal exposure to PCBs with human biomonitoring.ResultsA cross-sectional analysis indicated a significant negative effect of PCB exposure on HVA and VMA. Longitudinally, an initially higher exposure to higher chlorinated PCBs was followed by constant reduced HVA level over three consecutive years. Exploratory analyses show different long-term effects for different PCBs according to their chlorination degree. A higher exposure with lower chlorinated PCBs leads to an increase of VMA and HVA. Conversely, a higher exposure to all PCBs results in a reduction of HVA.ConclusionThis study, to our knowledge, is the first to document changes in neurotransmitter metabolites after occupational PCB exposure in humans. This finding advances evidence obtained from past research, and identifies one potential pathomechanism in the central dopaminergic system of humans.     

Bioaerosol exposure from composting facilities and health outcomes in workers and in the community: A systematic review update

Background

Rapid population growth and urbanisation around the world has led to increasing waste generation rates. Composting of organic waste in large-scale facilities is part of a growing trend in the UK, and elsewhere, to better manage and re-use the organic waste. However, composting inevitably generates bioaerosols, which have been associated with human health effects. In 2015, we reported that there was some, albeit limited, qualitative evidence linking bioaerosol emissions from composting facilities to poor respiratory health in nearby residents. However, the limited evidence precluded any quantitative assessment. Since then, the number of operational industrial-scale composting facilities in England has increased by 9% - nearly twice the growth from 2012 to 2014. At the same time, rapid urbanisation has led to expansion of city borders with more people living near large composting facilities and exposed to bioaerosol pollution. It is essential that regulatory authorities have access to the most up to date and accurate information.

The relevance of arguments for excluding ALAD from the recommended biological limit values in occupational exposure to inorganic lead (WHO 1980)

Summary Data on 394 simultaneous measurements of blood lead (PbB) and biological indicators of effect are considered with regard to dose-effect and dose-response relationships, as well as the association between the biological indicators of effect themselves. The indicators are delta-aminolevulinic acid dehydratase (ALAD) and zinc-protoporphyrin (ZPP) in blood, delta-amino-levulinic acid (ALAU) and coproporphyrin (CPU) in 24-h urine specimens. The specimens were taken from periodically controlled male workers moderately to excessively exposed to inorganic lead. In addition, data are presented on the spontaneous recovery of biological indicators in 14 male workers examined immediately after, approximately 4.5 months and 10 months after cessation of lead exposure. Highly significant (P<0.001) correlations were found between all of the indicators examined, with the following order of agreement with regard to PbB: ALAD>ZPP>ALAU>CPU. Comparative advantages of ALAD in typical (variable) occupational exposure conditions were found to include: (a) the highest sensitivity at both low and relatively high lead exposure levels, (b) better reflection of biologically active lead as opposed to PbB (particularly compared to ALAU and CPU), (c) higher specificity compared to other indicators of lead effect, and (d) generally higher reliability with regard to both biologically and methodologically induced variations. The data obtained undoubtedly demonstrate that urinary indicators ALAU and CPU are not sensitive enough for the recommended health-based occupational exposure limit, as defined by relatively low PbB concentration (WHO 1980). Despite possible theoretical considerations resulting in recommendations for ZPP and ALAU but excluding ALAD (WHO 1980), practical implications seem to be far more in favour of ALAD, which permits a maximal safety margin in preventing adverse effects in the entire work population because of its sensitivity and absence of time-lag with regard to lead exposure.Presented at the 20th International Congress on Occupational Health, Cairo, 25 September –1 October, 1981     

广东省艾滋病病毒职业性暴露应急系统响应情况分析

目的建立艾滋病病毒(HIV)职业性暴露应急系统,分析应急响应情况。方法回顾性收集和分析2002~2004年报告的广东省各地HIV职业性暴露个案。结果2002~2004年共报告152例HIV职业性暴露个案,其中医务人员占74.34%,干警占13.82%。29.61%是皮肤黏膜接触性暴露,70.39%是创伤性暴露。暴露级别中,一级暴露占57.24%,二级暴露占35.53%,三级暴露占7.24%。94.74%的暴露者进行了暴露后应急局部处理。发生暴露后,只有38.16%的暴露者采用了合理的处理方案。104例(68.42%)进行了预防性服药,但其中仅有27.88%(29/104)的人采用合理的服药方案。48例(31.58%)未进行预防性服药,但其中仅有60.42%(29/48)的人是真正无需预防性服药者。92例暴露者经12个月的随访未发现有感染HIV者。结论广东省HIV职业性暴露应急系统能有效地响应全省HIV职业性暴露事件,但仍需加强对职业性暴露后应急处理技术的知识培训。     

某综合医院66例医务人员血源性职业暴露调查分析

目的分析某综合医院医务人员发生血源性职业暴露情况,探讨针对性防护措施,减少职业暴露的发生。方法对某综合医院2010年1月1日～2010年12月31日上报登记的66例职业暴露进行分析。结果共收到66例医务人员发生血源性职业暴露报告。血源性职业暴露的人群集中于护士,占62.12%;工作年限低于5年者易发生职业暴露,占60.61%;锐器伤为导致暴露为主要形式,占到84.69%,致锐器伤操作环节多发生在输液、注射、采血后拔针时,占57.58%;所有职业暴露者均进行了紧急及相关干预处理,暂未发现因职业暴露而感染血源性传播疾病。结论增强医务人员职业暴露防护意识,规范操作规程,严格执行标准预防原则,采取有效预防措施,可预防或减少职业暴露的发生。     

The suitability of EBC-Pb as a new biomarker to assess occupational exposure to lead

Occupational exposure to lead (Pb) requires continuous surveillance to assure, as much as possible, safe and healthful working conditions. This study addresses the suitability of assessing Pb exposure in relevant workers using their exhaled breath condensate (EBC). This study enrolled workers of two different Pb processing industries characterized by moderate and high Pb exposure levels in the work environment, and a group of non-exposed individuals working in offices who served as baseline for Pb exposure. The EBC-Pb of workers reflected the Pb levels in the work environment of all three settings, although the relationship with B-Pb was not clear. The lack of correlation between EBC-Pb and B-Pb most probably indicates the time lag for Pb to enter in the two body pools. The EBC-Pb seems to reflect immediate exposure, providing a prompt signature of Pb in the environmental that may interact directly with the organ. By delivering short-term evaluation of exposure, EBC-Pb represents a clear advantage in biomonitoring and may become an interesting tool for estimating organ burden.     

Investigation of the relationship between low environmental exposure to metals and bone mineral density,bone resorption and renal function

Environmental exposure to metals has been linked to adverse health outcomes. Exposure to cadmium has been associated with decreased bone density, an increased risk of osteoporotic fracture and possible renal dysfunction. Older women are a group at risk of renal and bone density impacts and exposure to metals may be an important risk factor for these health outcomes. This study was a cross sectional study of 77 women aged 50 years and above examining the relationship between metals exposure and renal and bone health. Urinary and blood metals concentrations, plasma creatinine, iron, ferritin and transferrin were measured in these subjects. Bone biomarkers assessed included the pyridinium crosslinks, pyridinoline and deoxypyridinoline measured by ELISA. Renal function was assessed using eGFR and KIM-1. Whole body, hip and lumbar spine bone mineral density was assessed using DEXA. Blood and urinary metals concentrations were generally low in the subjects, with a median urinary cadmium concentration of 0.26 μg/g creatinine (range <0.065–1.03 μg/g). Urinary cadmium was found to be a significant predictor of bone mineral density at whole body, lumber spine, total hip and femoral neck, with increasing urinary Cd concentrations associated with decreased bone density. Urinary cadmium and aluminium concentrations were positively correlated with bone resorption whilst blood zinc and mercury concentrations were negatively correlated. Urinary aluminium was positively correlated with KIM-1 concentrations, a marker of early kidney damage, however blood zinc concentrations were significantly negatively correlated with this biomarker. This study provides additional support for low cadmium exposure being of concern for the health of older women. Further investigation into the role of exposure to other metals on bone and renal health is warranted.     

无锡市某私营铅蓄电池厂铅作业危害分析

目的监测与评价某私营铅蓄电池厂铅作业相关的职业病危害因素,为后续铅作业人员的个人防护和健康监护提供科学依据。方法采用现场调查方法了解该企业职业卫生管理现状,按GBZ159—2004、GBZ／T160．10～2004和GBZ2．1—2007等对工作场所中铅烟、铅尘进行检测和分析并结合职业健康检查分析影响工作人员血铅浓度的潜在因素。结果该企业存在铅烟、铅尘等职业病危害因素;铅烟、铅尘超标率为92．1％,铅作业人员血铅浓度增高比例为77．5％;铅作业人员血铅浓度与工龄、学历、下班前是否沐浴以及铅作业相关卫生知识知晓率有关（均P〈0．05）。结论该私营企业存在明显的铅作业危害,应改善工作环境,加强作业人员健康宣教及健康防护。     

Behaviour of biological indicators of cadmium in relation to occupational exposure

Summary Cadmium in blood (CdB), cadmium in urine (CdU) and beta2-microglobulins (2MU) were determined in 83 male workers exposed to cadmium fumes. CdU was measured both on 24-h urine samples and on spot samples. The behaviour of the biological indicators of cadmium was assessed in relation to degree of current exposure, length of exposure and cumulative exposure (computed as concentration of cadmium at the workplace multiplied by duration of exposure). CdB values were significantly higher in the subgroups of subjects with higher current cadmium exposure and in the subgroups of subjects with greater cumulative exposure, but the test levels were not influenced by duration of exposure. CdU levels were significantly higher in the subgroups of subjects with greater cumulative exposure, but were less influenced by current exposure or duration of exposure. Considering the entire population, a rather close correlation (r = 0.69) was observed between CdB and CdU. When the population was divided according to level of current exposure, a close relationship was observed between the two indicators in all subgroups; nevertheless, for identical CdU values, the CdB values were higher in the subjects with heavier current exposure. Even if in all Cd workers the 2MU levels were in the range of reference values, the highest 2MU levels were found in the subjects with CdU > 10 g/l. The data confirm that CdU is prevalently influenced by the body burden of metal, but they also suggest that the CdB levels are not influenced solely by the intensity of current exposure but also depend to a considerable degree on the body burden.     

肝胆外科护士职业暴露的危险因素分析及管理对策

目的 分析肝胆外科护士发生职业暴露的危险因素,针对相关危险因素采取切实可行的管理对策.方法 采用自行设计的“医护人员职业暴露调查表”对30名肝胆外科护士在2010年9月-2011年8月发生职业暴露的情况进行回顾性调查.结果 30名肝胆外科护士1年中发生锐器伤39例次,发生皮肤、黏膜被患者血液、体液、引流液接触暴露35例次;动静脉穿刺、拔针及拔针后处理不当、分离针头及整理用物、针头回套是发生锐器伤的高危环节;操作时未戴手套为皮肤黏膜接触暴露的主要原因;上午9:00-10:00、护士独立值班时、临床工作年限＜5年的护士是发生职业暴露的危险因素;护士对职业暴露相关知识及发生暴露后正确的处理流程知晓率低,护士的标准预防及手卫生依从性差.结论 通过对护士进行系统、规范的职业暴露相关知识培训,提高其对职业暴露的认识,针对存在的问题采取相应的措施,最大限度地降低护士职业暴露的风险,保障护理人员的职业安全.