瓷厂和钨矿粉尘危害性研究.pdf

华中科技大学硕士学位论文瓷厂和钨矿粉尘危害性研究姓名苏文进申请学位级别硕士专业劳动卫生与环境卫生学指导教师陈卫红 20080516 华中科技大学硕士学位论文华中科技大学硕士学位论文 1 英文缩写英文缩写 PAM pulmonary alveolar macrophage 肺泡巨噬细胞 LDH lactate dehydrogenase 乳酸脱氢酶 MTT methyl thiazolyl tetrazolium 噻唑蓝 ROS reactive oxygen species 活性氧簇 TNF-αα tumor necrosis factor-α 肿瘤坏死因子-α OD optical density 吸光度 SMR standardized mortality ratios 标化死亡比 COPD chronic obstructive pulmonary disease 慢性阻塞性肺病 IARC International Agency for Research on Cancer 国际肿瘤研究机构 TGF-β transing growth factor-β 转化生长因子-β RNS reactive nitrogen species 活性氮簇 ESR electron spin resonance 电子自旋共振 iNOS induced nitricoxide synthase 诱导型一氧化氮合成酶 IL interleukin 白介素 GM-CSF granulocyte-macrophage colony- stimulating factor 粒-巨噬细胞集落刺激因子 G-CSF granulocyte colony-stimulating factor 粒细胞集落刺激因子 IGF insulin-like growth factor 胰岛素样生长因子 PDGF platelet-derived growth factor 血小板源性生长因子独创性声明独创性声明本人郑重声明，本学位论文是本人在导师指导下进行的研究工作及取得的研究成果的总结。尽我所知，除文中已经标明引用的内容外，本论文不包含任何其他个人或集体已经发表或撰写过的研究成果。对本文的研究做出贡献的个人和集体，均已在文中以明确方式标明。本人完全意识到本人将承担本声明引起的一切法律后果。学位论文作者签名日期年月日学位论文版权使用授权书学位论文版权使用授权书本学位论文作者完全了解学校有关保留、使用学位论文的规定，即学校有权保留并向国家有关部门或机构送交论文的复印件和电子版，允许论文被查阅和借阅。本人授权华中科技大学可以将本学位论文的全部或部分内容编入有关数据库进行检索，可以采用影印、缩印或扫描等复制手段保存和汇编本学位论文。保密□ ，在_____年解密后适用本授权书。本论文属于不保密□。（请在以上方框内打“√” ）学位论文作者签名指导教师签名日期年月日日期年月日华中科技大学硕士学位论文华中科技大学硕士学位论文 2 瓷厂和钨矿粉尘危害性研究瓷厂和钨矿粉尘危害性研究学位申请人苏文进指导老师陈卫红教授摘摘要要生产性粉尘是指在生产过程中形成的，并能长时间漂浮在空气中的固体微粒。生产性粉尘不仅污染作业环境，而且对劳动者健康的损害也十分明显。既往研究表明粉尘可以直接或间接引发尘肺、慢性阻塞性肺病、肺心病、肺癌等多种疾病，并影响接尘作业工人的寿命。全世界大约近亿劳动者受到粉尘危害的影响。我国接触粉尘作业的人数众多，2000 年全国登记接尘人员超过 2000 万。此外，还有大量未登记却接触粉尘的私有企业人员或国有企业的农民合同工、轮换工。尘肺是由于在生产过程中长期吸入粉尘发生的以肺组织纤维化为主的疾病，是我国职业性疾病中所占比重最大、危害最严重的职业病，极大地威胁着从业人员的身心健康。据卫生部统计，至 2006 年底，中国尘肺累计病例数为 616442 例，死亡超过 14 万例，病死率近 24。目前，我国平均每年新增职业病患者 1.5 万人左右，其中新增尘肺病 1.2 万人。如果不加以干预，预计到 2015 年尘肺病例将达到 72 万。生产场所中粉尘类型众多，有研究发现，不同类型的粉尘致病能力很不一致，即使是同类型的粉尘，如果来源不同（如不同来源的商业性石英），其损伤和活化肺泡巨噬细胞（PAM）的程度也很不相同[1]。在我研究组前期对广西锡矿生产性粉尘的生物学活性研究中发现，矿山粉尘对 PAM 的细胞毒性及致纤维化能力，与人群流行病学研究发现的接尘工人标化死亡率和矽肺发病率存在一致性趋势。为验证前期研究的结果，进一步评价我国陶瓷行业和金属矿山（钨矿）粉尘的生物学活性，及对接尘工人健康的影响，本研究收集 4 个瓷厂（江西 3 个，湖南 1 个）和 4 个钨矿（湖南 1 个，江西 3 个）历史监测资料和作业场所粉尘样本，对以往建立的接尘工人队列继续随访至 2003 年底，分析接尘对工人寿命的影响。本研究共分为三部分一、瓷厂及钨矿华中科技大学硕士学位论文华中科技大学硕士学位论文 3 粉尘的监测与分析；二、粉尘的生物学活性评价；三、瓷厂及钨矿队列接尘工人主要死因分析。第一部分第一部分瓷厂和钨矿职业危害粉尘的监测瓷厂和钨矿职业危害粉尘的监测收集陶瓷厂和钨矿作业场所粉尘历史监测资料，结合现场粉尘测定，全面分析陶瓷厂和钨矿粉尘危害的严重程度和变化情况，为同类企业制订防护措施提供科学依据。本研究 4 个瓷厂及 4 个钨矿的粉尘监测分别始于 1972 年和 1958 年，对于以前缺乏记录的环境监测资料，由测尘员、工业卫生人员、经验丰富的工人以及安全技术工程人员根据当时的工作条件，并结合我国的降尘防尘措施、生产工艺改革等情况进行估算。监测项目包括粉尘浓度、游离二氧化硅含量、分散度和粉尘各种元素含量。为了保证监测的准确性，于 1987-1988 年和 2005-2006 年对瓷厂和钨矿作业场所进行了现场监测。结果表明（1）瓷厂作业场所空气中的平均总粉尘浓度在二十世纪五十年代高达 16.1 mg/m3，以后逐年下降，六十年代到八十年代平均总粉尘浓度维持在 10 mg/m3～ 12 mg/m3左右，八十年代末降至 10 mg/m3以下，1993 年为 3.8 mg/m3，2004 年为 1.6 mg/m3；钨矿作业场所空气中的平均总粉尘浓度在二十世纪五十年代后期高达 13.3mg/m3，五十年代末迅速下降，1958 年平均总粉尘浓度达到 5.7 mg/m3，以后缓慢下降，七十年代初在 2.4 mg/m3左右，此后直到 2004 年，粉尘浓度整体变化不大，在 2.0 mg/m3左右，2004 年平均总粉尘浓度为 1.4 mg/m3。但是总体而言，这两类厂矿的平均总粉尘浓度仍超过我国现行工作场所空气中粉尘容许浓度标准（1mg/m3）。（2）瓷厂积尘的平均游离二氧化硅的含量为 30左右，而钨矿为 50左右，高于瓷厂；瓷厂呼吸性粉尘的游离二氧化硅含量为 26.37，而钨矿为 39.48，高于瓷厂。（3）粉尘分散度测定结果显示，瓷厂总粉尘中粒径小于 10m 的尘粒占 73.45，钨矿的占 84.65；瓷厂总粉尘中粒径小于 5m 的尘粒占 29.46，钨矿的占 56.7。华中科技大学硕士学位论文华中科技大学硕士学位论文 4 瓷厂粉尘的分散度低于钨矿。（4）瓷厂积尘的砷、镍、镉、铁、铜、锰元素的平均含量分别为 18.2、8.7、2.0、 5957.0、 24.0、 417.7g/g，而钨矿的分别为 102.9、 20.4、 17.9、 19067.9、 907.7、 1201.4g/g，均高于瓷厂；瓷厂积尘中的铝元素平均含量为 22373.3g/g，大于钨矿的 12618.5g/g。第二部分第二部分粉尘的生物学活性测定粉尘的生物学活性测定本部分通过测定瓷厂和钨矿粉尘的理化特性和粉尘的生物学活性（包括细胞毒性、产生活性氧的能力和致纤维化能力），分析陶瓷和钨矿粉尘的细胞毒性和产生活性氧及致纤维化能力，从而为粉尘作业危害评价提供依据。采集上述 4 个瓷厂（以 A、B、C 及 D 厂表示）及 4 个钨矿（以 E、F、G 和 H 矿表示）不同作业点的粉尘样品，测定其理化特性（包括粉尘的分散度及粉尘化学元素含量分析）；以豚鼠的 PAM 为试验对象，以中国标准石英粉尘为阳性对照，用不同浓度的粉尘染毒，通过乳酸脱氢酶活力、细胞活力、活性氧释放量及 TNF-α 释放量的测定来评价粉尘样品的生物学活性。结果显示（1）与钨矿粉尘相比，瓷厂的粉尘样品铝含量较高，而钨矿粉尘中的砷、铁、锰等元素的含量要明显高于瓷厂的粉尘。不同类型的厂矿，甚至同一类型厂矿不同作业点的粉尘之间化学元素含量差别较大。（2）瓷厂及钨矿粉尘样本在各浓度下均能导致 LDH 酶活性的增强（粉尘的直接细胞毒性），且有明确的剂量反应关系。D 厂、E 矿和 F 矿粉尘样品诱导 LDH 酶活性的能力较强。不同瓷厂粉尘之间诱导的 LDH 酶活性的差异较小，而钨矿的差异则较大。（3）随着各粉尘样品及对照粉尘浓度的增高，PAM 的活力呈下降趋势。四个瓷厂的粉尘样品所致 PAM 活力的改变与阳性对照接近，而钨矿粉尘所致 PAM 活力的改变低于阳性对照。（4）瓷厂和钨矿粉尘（除 H 厂之外）及对照所致 PAM 活性氧的释放随着粉尘浓度的升高呈明显的上升趋势，并且这七个厂矿的粉尘样品诱导 PAM 释放活性氧的能华中科技大学硕士学位论文华中科技大学硕士学位论文 5 力都与对照较为接近。H 厂粉尘诱导 PAM 活性氧的能力较弱，并且活性氧的释放量与粉尘浓度无明显的剂量反应关系（5）瓷厂和钨矿粉尘样品在各浓度下均能诱导 PAM 释放 TNF-α。除了 H 矿在各浓度下诱导 TNF-α 的能力都较强外，其余各种粉尘样品及对照诱导的 TNF-α 均随着粉尘浓度的升高而增加。C 厂和 H 矿粉尘样品诱导 TNF-α 的能力较强，而 E 矿的较弱。瓷厂粉尘在低浓度（15、30、60g/106个细胞）下诱导 PAM 释放 TNF-α 的能力低于钨矿粉尘，但是在最高浓度（120g/106个细胞）下诱导 PAM 释放 TNF-α 的能力却明显高于钨矿粉尘。第三部分第三部分瓷厂及钨矿队列人群死因分析瓷厂及钨矿队列人群死因分析通过对陶瓷厂和钨矿队列人群的主要死亡原因进行分析，找出危害陶瓷工人和钨矿工人健康和寿命主要疾病，探讨粉尘的生物学活性与其对接触人群损害之间的可能联系。以上述4个瓷厂和4个钨矿1972年1月1日至1974年12月31日在册且工作一年以上的工人为研究对象建立队列，随访至2003年底，对所有死亡的队列成员进行死因分析，以卫生部公布的城市全国人群年龄别死亡率为对照计算标化死亡率。结果（1）4个瓷厂人群共4957人，其中男性3648人，女性1309人，追访至2003 年底，合计130783.6人年，全死因标化死亡率（SMR）比为1.01，主要疾病按累计死亡率从高到低顺序排列依次为肿瘤（6.56）、心血管疾病（6.54）、呼吸系统疾病（5.71）、脑血管疾病（4.72）。死亡超过全国平均水平的主要有矽肺、传染性疾病、肺结核和呼吸系统疾病，其SMR分别为36.35、5.08、4.06和1.30，其中，矽肺的死亡尤其突出。（2） 4个钨矿人群共12978人，其中男性11673人，女性1305人，追访至2003年底，合计336417.8人年；全死因标化死亡比（SMR）为1.18，主要疾病按累计死亡率从高到低顺序排列依次为心血管疾病（9.22）、呼吸系统疾病（7.30）、肿瘤（6.03）、肺结核4.73；死亡超过全国平均水平的有矽肺、肺结核、呼吸系统疾病、肝癌等， SMR分别为65.27、3.90、1.90及1.38。华中科技大学硕士学位论文华中科技大学硕士学位论文 6 结结论论本研究在4个瓷厂和4个钨矿队列研究的基础上，从职业粉尘危害的监测、粉尘的生物学活性及队列人群的死因分析三方面综合分析粉尘对健康的影响，得出以下主要结论（1）瓷厂和钨矿的平均总粉尘浓度在五十年代初期超过 13 mg/m3，从五十年代末期开始，都有明显下降，到 2004 年已降至 1.5 mg/m3左右，说明在瓷厂和钨矿实行的工艺改革和综合防尘降尘措施效果显著。（2）粉尘生物学活性与其导致接尘人群危害之间存在一致性趋势前期队列研究表明，瓷厂和钨矿粉尘对接尘工人的寿命影响明显，而两类粉尘致细胞膜损伤及细胞活力的改变较为明显，这与前期人群研究结果一致；其中，钨矿粉尘对 PAM 细胞膜毒性略高于瓷厂粉尘，而对细胞活力的影响小于瓷厂粉尘，这可能是粉尘元素含量的不同造成的。 ROS 诱导的 DNA 损伤，可能是诱发突变的基础，两种厂矿的粉尘诱导 ROS 的能力都较强，高于对照标准石英，这与两类厂矿接尘工人肿瘤累积死亡率高相一致。 TNF-α 在肺纤维化过程中起重要作用，本研究结果显示瓷厂和钨矿粉尘致细胞释放 TNF-α 水平高，与两类型厂矿很高的矽肺 SMR 相对应。钨矿粉尘在中、低粉尘浓度下诱导 TNF-α 的能力都要强于瓷厂粉尘和标准石英，且历年钨矿粉尘的游离二氧化硅含量和分散度均高于瓷厂粉尘，这也许是尽管瓷厂历年粉尘浓度高于钨矿，但是钨矿矽肺 SMR 仍明显高于瓷厂矽肺 SMR 的原因之一。小小结结本研究通过选择有代表性的4个瓷厂和4个钨矿，结合厂矿队列研究发现两类厂矿的粉尘对工人的健康危害明确，两类厂矿历年粉尘浓度超过国家职业卫生标准，两类厂矿粉尘均有明确的细胞损伤作用，对接尘工人寿命和健康有明确影响；瓷厂队列人群矽肺死亡率是全国平均水平的36.35倍，钨矿的为65.27倍，与这些厂矿粉尘的致纤华中科技大学硕士学位论文华中科技大学硕士学位论文 7 维化能力一致。两厂矿粉尘均能诱导PAM释放ROS，这与两类厂矿接尘工人肿瘤，特别是肺癌和肝癌高发的现象是一致的。本研究在队列研究的基础上，结合粉尘的生物学活性进行分析，以期为今后开展厂矿粉尘危害性研究提供参考。关键词关键词粉尘；尘肺；矽肺；理化特性；细胞毒理学；分散度；游离二氧化硅；化学元素；生物学活性；SMR分析；华中科技大学硕士学位论文华中科技大学硕士学位论文 8 The Study on the Hazard of Occupational Dusts of Pottery Factories and Tungsten Mines Abstract The workplace dust is usually referred to as solid particulates ed during production and can stay in the air for a long time. The productive dusts not only pollute the environment, but also affect the health of employees. er studies suggested that dusts have been associated directly or indirectly with the development of silicosis, chronic bronchitis, chronic obstructive pulmonary disease COPD, and lung cancer in workers, and shorten the life span of workers. The number of workers exposed to dust is about 100,000,000 globally. In China, the dust-exposed workers in registration had reached 20,000,000 by 2000, though the number was only an angle of the iceberg since it did not include dust-exposed workers in personal enterprises and inal workers and casual workers in state-owned enterprises. Pneumoconiosis is a fibrotic disease of the lungs produced by the inhalation and deposition of dust. It is of serious damage to the health of workers and takes the largest proportion in the occupational diseases in China. According to the Health Ministry, by 2006 the number of accumulative cases of pneumoconiosis has researched 616,442, and the mortality was 24, which meant that more than 140,000 cases had died. If no interference was rted, the number of silicosis patients would reach 720,000 by 2015. There are many types of productive dusts. Exposure to the different types of dusts can result in different outcomes. Even for dusts with the same type but of different sources, like commercial quartzes of different sources, their abilities to damage and activate PAM Pulmonary Alveolar Macrophage were different [1]. Our er study on tin dust particles found that the results from in vitro tests were in accordance with epidemiological reports in a cohort study of four tin mines, which showed increased mortality of all cancers and lung cancer and elevated pneumoconiosis risk. To testify the result of the er research, and further assess the bioactivity of dusts from pottery industry and metal mines tungsten 华中科技大学硕士学位论文华中科技大学硕士学位论文 9 mines and their impacts on the health of dust-exposed workers, historical dust monitoring data and dust samples from 4 pottery factories 3 in Jiangxi Province and 1 in Hunan Province and 4 tungsten mines 1 in Hunan Province and 3 in Jiangxi Province were collected. And the follow-up of er-established cohorts was continued till the end of 2003 and the SMRs of different diseases were analyzed. The research includes three parts 1 The monitoring and the analysis of the productive dusts from pottery factories and tungsten mines. 2 The assessment of the bioactivities of the dust particles. 3 The SMR analysis of dust-exposed workers in pottery factories and tungsten mines. Part 1 The Monitoring and the Analysis of Productive Dusts from Pottery Factories and Tungsten Mines Through collecting historical dust-monitoring data of working places in pottery factories and tungsten mines, combining the dust determinations in work sites, the change of dust concentrations and particle distribution in the pottery factories and tungsten mines from 1952 or 1972 to 2004 were analyzed. The study aimed to provide scientific evidence for the enacting of the dust control and protection measures for the same kind of industries. Dust monitoring in these 4 pottery factories and 4 tungsten mines started in 1972 and 1958 respectively. For missing data before 1972 in pottery factories and before 1958 in tungsten mines, consensus estimates were made by industrial hygiene experts, public local supervisors based on the history of control measures and major changes in technical processes in the factories and mines. The items of dust monitoring included the dust concentrations, the free silica containment in the dusts, the dispersity of the dusts and the elements in the dusts. To ensure the quality of the monitoring data, dust monitoring was organized in the working sites of pottery factories and tungsten mines during 1987-1988 and 2005-2006. The results showed that 1 In 1950s the average total dust concentration of pottery factories was as high as 16.1 mg/m3,and it maintained between 10 and 12 mg/m3 from 1960s to 1980s. In the end of 1980s, the concentration was below 10 mg/m3, and it was 3.8 and 1.6 mg/m3 in 1993 and 2004 respectively. The average total dust concentration of 华中科技大学硕士学位论文华中科技大学硕士学位论文 10 tungsten mines in the end of 1950s was 13.3 mg/m3, and it fell to 5.7 mg/m3 in 1958. And after that, the concentration continued to decline. The concentration was around 2.4 mg/m3 in the early 1970s, and was 1.4 mg/m3 in 2004. Despite of the improvement in the dust-control of these two types of industries, the average concentrations were still beyond the Chinese National Standard of dust concentrations in workplace 1mg/m3. 2 For pottery factories and tungsten mines, the free silica containment was around 30 and 50 in the collected dusts and was 26.37 and 39.48 in the respirable dusts respectively. In a whole, the free silica containment was higher in the tungsten dusts. 3 The analysis of the dispersity of the dusts showed that the proportion of the dusts with a diameter less than 10m was 73.45 and 84.65 for the pottery factories and tungsten mines respectively, and it was 29.46 and 56.7 for dusts with a diameter less than 5m respectively. 4 The average containment of As, Ni, Cd, Fe, Cu and Mn elements in pottery collected dusts was 18.2、8.7、2.0、5957.0、24.0 and 417.7g/g respectively and the above elements were richer in tungsten collected dusts namely 102.9、 20.4、 17.9、 19067.9、 907.7 and 1201.4g/g. The Al containment in the pottery collected dusts was 22373.3g/g, almost twice of that in tungsten collected dusts. Part 2 The Assessment of the Bioactivities of the Dusts from Pottery Factories and Tungsten Mines To uate the role of in vitro study in the assessment of the dust hazard, and provide base for assessing the occupational hazards in the dust-exposed working places by analyzing the physic-chemical characteristics and assessing the bioactivities of dusts from pottery factories and tungsten mines. Dusts from different working places in above 4 pottery factories namely A, B, C and D factories and 4 tungsten mines namely E, F, G and H mines were analyzed for the physic-chemical characteristics. And the LDH activity, cell viability, ROS and TNF-α release of guinea pig PAM were chosen to assess the bioactivities of dusts by using China Standard Quartz as control. 华中科技大学硕士学位论文华中科技大学硕士学位论文 11 The results showed that 1 The Al in pottery dusts was richer, while the As, Fe and Mn etc were richer in tungsten dusts. The element containments were different between even among dusts of the same kind. 2 Dose-response relationship between the enhancement of LDH activity and the dust concentration was found in both dusts from pottery factories and tungsten mines. Stronger ability to induce LDH activity was found in dusts from D, E and F factories mines and the variability to enhance LDH activity was small in pottery factories but was comparatively great in tungsten mines. 3 The cell viability decreased as the dusts’ concentrations increased. The cell viabilities induced by pottery dusts were similar to that of control; while those induced by tungsten dusts was a bit lower than that of control. 4 Except for dusts from H mine, dose-response relationship was found between dust concentrations and the release of ROS. The ability of H mine to induce the release of ROS was lower than that of control while the other dusts were of the similar ability compared with the control. 5 The ability to induce TNF-α was found in all the dusts under all the concentrations. Except for dusts from H mine, which could induce relatively high dose of TNF-α under every set concentration, dose-response relationship was found between dust concentrations and the releases of TNF-α. Compared with the control, the dusts from C factory and H mine were easier to induce the release of TNF-α while the dust from E mine was on the contrary. Totally, except for the highest dust concentration120g/ 106 cells, the dusts fr