【作者】 苏文进；

【导师】 陈卫红；

【作者基本信息】 华中科技大学 ， 劳动卫生与环境卫生学， 2008， 硕士

【摘要】 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/m~3,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/m~3～12 mg/m~3左右,八十年代末降至10 mg/m~3以下,1993年为3.8 mg/m~3,2004年为1.6 mg/m~3;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/m~3,五十年代末迅速下降,1958年平均总粉尘浓度达到5.7 mg/m~3,以后缓慢下降,七十年代初在2.4 mg/m~3左右,此后直到2004年,粉尘浓度整体变化不大,在2.0 mg/m~3左右,2004年平均总粉尘浓度为1.4 mg/m~3。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/m~3)。(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10μm的尘粒占73.45%,钨矿的占84.65%;瓷厂总粉尘中粒径小于5μm的尘粒占29.46%,钨矿的占56.7%。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、417.7μg/g,而钨矿的分别为102.9、20.4、17.9、19067.9、907.7、1201.4μg/g,均高于瓷厂;瓷厂积尘中的铝元素平均含量为22373.3μg/g,大于钨矿的12618.5μg/g。第二部分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、60μg/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(120μg/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。结论本研究在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。更多还原

【Abstract】 The workplace dust is usually referred to as solid particulates formed 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. Former 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 informal 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 exerted, 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 former 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 former research, and further assess the bioactivity of dusts from pottery industry and metal mines (tungsten 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 former-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 MinesThrough 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 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 10μm 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 5μm 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 417.7μg/g respectively and the above elements were richer in tungsten collected dusts namely 102.9、20.4、17.9、19067.9、907.7 and 1201.4μg/g. The Al containment in the pottery collected dusts was 22373.3μg/g, almost twice of that in tungsten collected dusts.Part 2 The Assessment of the Bioactivities of the Dusts from Pottery Factories and Tungsten MinesTo evaluate 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-αrelease of guinea pig PAM were chosen to assess the bioactivities of dusts by using China Standard Quartz as control. 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-αwas found in all the dusts under all the concentrations. Except for dusts from H mine, which could induce relatively high dose of TNF-αunder 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-αwhile the dust from E mine was on the contrary. Totally, except for the highest dust concentration(120μg/ 106 cells), the dusts from tungsten mines were more able to induce TNF-αthan those from pottery factories under the other concentrations (15、30 and 60μg/ 106 cells).Part 3 The Standardized Mortality Rate Analysis of Workers from Pottery Factories and Tungsten MinesThis part aimed to find the main diseases endangering the health and the life span of workers from pottery factories and tungsten mines, and provide instructions for the health care of the workers in these industries by the SMR analysis of workers from cohorts of pottery factories and tungsten mines.Cohorts were established basing on the above pottery factories and tungsten mines by choosing workers registered during Jun 1st 1972 and Dec 31st 1974 and with at least one working year. The cohorts were followed-up till the end of 2003 and the causes of death were analyzed and the SMR was calculated based on the domestic agespecific mortality from Health Ministry.Results (1) The number of workers in pottery factories was 4957, among which 3648 were males and 1309 were females. Totally 130783.6 person-years was calculated till the end of 2003. The main diseases caused the death were cancer (6.56%), cardiovascular diseases (6.54%), respiratory diseases (5.71%) and vascular diseases (4.72%) by the cumulative mortality. The diseases with the mortalities above the domestic level were namely silicosis, infective diseases, tuberculosis, and respiratory diseases, and their SMRs were namely 36.35, 5.08, 4.06 and 1.30.(2) The number of workers in tungsten mines was 12978, among which 11673 were males and 1305 were females. Totally 336417.8 person-years was calculated till the end of 2003. The main diseases caused the death were cardiovascular diseases (9.22%), respiratory diseases (7.30%), cancer (6.03%) and tuberculosis (4.73%) by the cumulative mortality. The diseases with the mortalities above the domestic level were namely silicosis, tuberculosis, respiratory diseases and liver cancer, and their SMRs were namely 65.27、3.90、1.90and1.38.ConclusionsBased on the cohorts of 4 pottery factories and 4 tungsten mines, the occupational dust hazard monitoring, the bioactivity of dusts and the SMR analysis of the cohorts were analyzed in the research to study the impacts of dust on health. And several conclusions were drawn as follows:(1) The average total dust concentration was higher than 13 mg/m3 in both pottery factories and tungsten mines in the early 1950s. And the concentrations have fallen obviously since the end of 1950s, and they were around 1.5 mg/m3 in 2004. This suggested that the reform in the working procedure and the combined dust proof and protection measures were of great efficiency.(2) The bioactivities of the dusts were in line with the impacts that they brought on the health of the dust-exposed workers.The changes in the LDH activity and cell viability by both types of dusts were obvious, indicative of their strong cytotoxicity, and these were coherent with the former cohort studies on dust-exposed workers of pottery factories and tungsten mines which found that the dusts from these two industries could obviously affect the health of the dust-exposed workers. Compared with the pottery dusts, the tungsten dusts were a bit higher in the membrane cytotoxicity to PAM but lower in the impact on the cell viability of PAM, probably due to the variability of the element containments in the dusts.The DNA impairments induced by ROS might be the base of mutation. Strong ability to induce ROS in PAM by both types of dusts compared with the control was found in this study, and this might contribute to the high incidence of cancer in both pottery factories and tungsten mines.TNF-αhas been found to play an important role in the process of the lung fibrosis. In this study, stronger ability to induce TNF-αunder lower concentrations (15, 30,60μg/106 cells) was found in tungsten dusts, more respresentative of the actual dust concentrations in the workplaces. Besides, higher containment of the free silica and higher disperity in tungsten dusts were also found in the monitoring data, these would be help to understand why higher SMR of silicosis was found in tungsten workers compared with that of pottery workers despite of higher average dust concentrations in the pottery mines.SummaryObvious threat of these two types of dusts to workers health was observed by selecting dust samples from 4 pottery factories and 4 tungsten mines on the base of the cohort studies of these factories/mines. The average dust concentrations of these factories/mines were beyond the Chinese National Standard of dust concentrations in workplace. Definite cytotoxicity on PAMs and obvious impacts on the health and lifespan of dust-exposed workers by these two types of dusts were observed in this study. The SMRs of silicosis in the cohorts of these pottery factories and tungsten mines were 36.35 and 65.27 respectively, which were in accord with fibrogenic ability of their dusts. The ability to induce ROS was found in both two types of dusts, and this concorded with the high prevalence of cancers especially lung cancer and hepatoma in these cohorts. By the bioactivity analysis of dusts based on the cohort study, this research aimed to provide reference for future studies on the hazard of dusts from similar factories/mines.更多还原