职业接触可溶性铬盐个体暴露与尿铬水平的相关性研究

目的通过对职业接触可溶性铬盐个体暴露与尿铬水平的相关性研究,探讨并提出可溶性铬盐职业接触者尿铬生物限值,为铬盐职业接触人群健康监护和危险性评价提供依据。方法通过流行病学横断面调查,以不同剂量铬盐接触的83名劳动者为研究对象,10名非铬盐接触的农民为对照,两组人群在年龄、性别和吸烟状况等方面相匹配,进行了个体铬盐暴露与班末尿铬含量的研究,并对二者之间的关系进行了分析。同时复习了对可溶性铬盐职业接触者尿铬生物限值的相关文献。结果对照组8 h个体空气铬连续监测浓度在0.00~0.08μg/m3之间,尿铬浓度经肌酐校正后在0.40~1.02μg/g肌酐之间。铬盐接触劳动者8 h连续空气个体监测浓度在0.10~287.00μg/m3之间,尿铬浓度范围在1.14~79.07μg/g肌酐。职业接触铬盐工人班末的尿铬浓度随个体铬盐暴露水平的增加而增加,两者具有相关性。其回归方程为尿铬浓度(μg/g肌酐)=4.16+236.86×空气中铬的浓度(mg/m3),尿铬与空气铬的浓度相关系数r=0.976。通过文献复习,美国政府职业卫生工作者协会(ACG IH)推荐的职业接触可溶性铬盐在与我国相同的时间加权平均阈限值0.05mg/m3下,尿铬生物接触限值为65.1μmol/mol肌酐(30μg/g肌酐)。结论职业接触可溶性铬盐工人班末的尿铬含量可以用来评价作业场所铬盐的接触情况。依据美国ACG IH推荐的生物接触限值以及本调查结果,作者提出连续工作5个工作日的工作周末/班末尿铬的推荐值为65.1μmol/mol肌酐(30μg/g肌酐)。     

Mineral fibres, fibrosis, and asbestos bodies in lung tissue from deceased asbestos cement workers.

Lung tissue from 76 deceased asbestos cement workers (seven with mesothelioma) exposed to chrysotile asbestos and small amounts of amphiboles, has been studied by transmission electron microscopy, together with lung tissue from 96 controls. The exposed workers with mesothelioma had a significantly higher total content of asbestos fibre in the lungs than those without mesothelioma, who in turn, had higher concentrations than the controls (medians 189, 50, and 29 x 10(6) fibres/g (f/g]. Chrysotile was the major type of fibre. The differences were most pronounced for the amphibole fibres (62, 4.7, and 0.15 f/g), especially crocidolite (54, 1.8 and less than 0.001 f/g), but were evident also for tremolite (2.9, less than 0.001, and less than 0.001 f/g) and anthophyllite (1.7, less than 0.001, and less than 0.001 f/g). For amosite, there was no statistically significant difference between lungs from workers with and without mesothelioma; the lungs of workers had, however, higher concentrations than the controls. Strong correlations were found between duration of exposure and content of amphibole fibres in the lungs. Asbestos bodies, counted by light microscopy, were significantly correlated with the amphibole but not with the chrysotile contents. Fibrosis was correlated with the tremolite but not the chrysotile content in lungs from both exposed workers and controls. Overall, similar results were obtained using fibre counts and estimates of mass.     

Mineral fibres, fibrosis, and asbestos bodies in lung tissue from deceased asbestos cement workers

Lung tissue from 76 deceased asbestos cement workers (seven with mesothelioma) exposed to chrysotile asbestos and small amounts of amphiboles, has been studied by transmission electron microscopy, together with lung tissue from 96 controls. The exposed workers with mesothelioma had a significantly higher total content of asbestos fibre in the lungs than those without mesothelioma, who in turn, had higher concentrations than the controls (medians 189, 50, and 29 x 10(6) fibres/g (f/g]. Chrysotile was the major type of fibre. The differences were most pronounced for the amphibole fibres (62, 4.7, and 0.15 f/g), especially crocidolite (54, 1.8 and less than 0.001 f/g), but were evident also for tremolite (2.9, less than 0.001, and less than 0.001 f/g) and anthophyllite (1.7, less than 0.001, and less than 0.001 f/g). For amosite, there was no statistically significant difference between lungs from workers with and without mesothelioma; the lungs of workers had, however, higher concentrations than the controls. Strong correlations were found between duration of exposure and content of amphibole fibres in the lungs. Asbestos bodies, counted by light microscopy, were significantly correlated with the amphibole but not with the chrysotile contents. Fibrosis was correlated with the tremolite but not the chrysotile content in lungs from both exposed workers and controls. Overall, similar results were obtained using fibre counts and estimates of mass.     

某铬酸盐厂接触铬及其化合物职工铬鼻病的患病情况

目的了解栾城县某铬酸盐厂的职业卫生现状,有效控制由于铬酸盐危害而导致的铬鼻病的发生。方法对该厂铬酸盐粉尘浓度进行检测,对接触铬及其化合物的工人(接触组)和其它岗位的人员(对照组)进行健康检查后比较其铬鼻病的患病率。结果车间铬酸盐粉尘浓度为0.054mg/m3,超过国家规定的车间空气中铬酸盐的最高容许浓度(0.05mg/m3);健康检查接触组和对照组铬鼻病患病率分别为45.6%和22.6%,差异有统计学意义(χ2=13.78,P0.01)。结论某铬酸盐厂的主要职业病危害因素是铬酸盐粉尘,根据其对防尘除尘设施不到位现状,应加大职业卫生监督检查力度,普及职业病防治知识,提高工人对铬鼻病的认识和自我保护能力,保护劳动者的健康。     

Toxicity of hexavalent chromium to the alveolar macrophage in vivo and in vitro

In vivo and in vitro systems were used to evaluate hexavalent chromium toxicity to alveolar macrophages. Rat alveolar macrophages were exposed to 2 micrograms calcium chromate (CaCrO4, insoluble) or 2 micrograms chromium trioxide (CrO3, soluble) in live animals, in vivo, and in tissue culture, in vitro, collected by lavage from the lung. Chemiluminescence and oxygen consumption were measured as indicators of toxicity. Trypan blue dye exclusion was used to determine macrophage viability. In vivo exposure of the macrophage to either chromium compound showed no toxic effects at a 2-micrograms dose. Macrophages exposed in tissue culture, however, had values significantly different from controls. The untreated controls for both exposure methods were compared to evaluate differences resulting from methods alone.     

红细胞中铬含量作为铬盐接触者生物标志物的研究

目的通过对职业接触可溶性铬盐劳动者红细胞中铬浓度的研究,了解红细胞中铬浓度与个体环境可溶性铬盐接触之间的相关性及其在职业人群中分布的特点、影响因素,探讨其作为职业接触可溶性铬盐接触性生物标志物的可行性。方法采用横断面现场研究,对山东省济南市某铬盐生产企业进行了流行病学调查。接触组选择重铬酸钾制造业铬盐作业劳动者114名(男74名、女40名);年龄范围25~52岁,平均年龄(35.83±6.14)岁;工龄1~37年,平均工龄(14.20±6.77)年;接触铬盐年限范围0.5~28年,平均接触铬盐年限(9.80±5.97)年。对照组为无毒物接触史的健康人员30名(男22名,女8名),年龄范围25~47岁,平均年龄(36.13±6.17)岁。接触组与对照组两组人群在年龄、性别和吸烟状况等方面相匹配。通过问卷调查了解研究对象的一般情况、职业接触情况、吸烟饮酒情况、既往疾病史、个人防护情况等。作业环境铬盐浓度的测定:采用双滤膜个体采样器8 h工作日连续采样,滤膜铬盐含量采用火焰原子吸收分光光度法测定;红细胞中铬浓度测定采用石墨炉原子吸收分光光度法;血浆还原能力测定采用二苯碳酰二肼分光光度法;总维生素C、还原型维生素C含量的测定采用2,4二-硝基苯肼法。用SPSS10.0统计软件进行单因素统计分析和多元回归分析。结果职业接触可溶性铬盐劳动者红细胞中铬浓度为(15.79±31.01)μg/L,高于对照组的(3.21±2.20)μg/L,差异有统计学意义。当空气中个体铬盐暴露浓度小于106.00μg/m3时,职业接触可溶性铬盐劳动者红细胞中铬浓度随个体铬盐接触水平的增加而增加,并呈明显的剂量-反应关系。相关分析结果表明:红细胞中铬浓度与空气中个体铬盐暴露水平之间呈显著的正相关。多元回归证实:在α=0.10水平,血浆中维生素C、血浆六价铬的还原能力可以作为可溶性铬盐接触氧化应激水平的指标,并可影响红细胞内铬的摄取。结论红细胞中铬含量可以作为可溶性铬盐职业接触者的有效接触性生物标志物,尤其适于个体低剂量铬盐接触的评价。     

Effects of chronic chromate exposure on human serum prostate specific antigen: a cross sectional study

The detrimental effect of chronic chromium (Cr) exposure on the prostate has never been studied. Here, we report the prostate specific antigen (PSA) changes in occupational chromate exposed workers. In this study, eighty six male occupational chromate exposed workers and forty five age-matched controls were recruited. The concentration of Cr in urine (U-Cr), serum total PSA (tPSA), free PSA (fPSA), high sensitive C reactive protein (Hs-CRP) and peripheral white blood cells count (WBC) were measured. The results show that the U-Cr, serum tPSA, Hs-CRP and WBC were significantly higher in Cr exposed workers when compared to the controls. Contrastively, the serum fPSA level in Cr exposed workers was lower than controls. A significant positive correlation between U-Cr and serum tPSA was observed. Multiple linear regression analysis revealed that serum tPSA and fPSA level was statistically associated with the serum Hs-CRP and U-Cr concentration in Cr exposed workers. These observations suggested that chronic Cr exposure could produce potential prostate injury and the nonspecific inflammation at least might be one of the reasons to explain the elevated concentration of tPSA in chronic occupational chromate exposed workers.     

Exposure to hexavalent chromium does not increase 8-hydroxydeoxyguanosine levels in Korean chromate pigment workers.

This study was performed to determine whether chromium exposure increased 8-hydroxydeoxyguanosine levels in respiratory epithelial and white blood cells of chromate pigment workers. The subjects of this study were 22 chromium pigment workers and 16 controls in a chromate pigments factory. To estimate the level of exposure, hexavalent chromium concentrations in the factory air were measured. Chrominum concentrations of venous blood and spot urine, and 8-hydroxydeoxyguanosine levels in DNA extracted from sputum and white blood cells were determined. Correlation coefficients were calculated between them and their statistical significance was tested. Hexavalent chromium concentration in the factory air ranged from below limit of detection to 0.5150 mg/m3. Chromium levels in blood and 8-hydroxydeoxyguanosine levels in DNA extracted from venous blood and sputum were not statistically different between the two groups. Urine chromium level was significantly higher among workers. Among the correlation coefficients between blood chromium concentration, urine chromium concentration, blood 8-OH-dG level, and sputum 8-OH-dG level, none was statistically significant for workers, controls, and total subjects. Duration of employment did not show any significant correlation with those four variables, either. These results suggest that neither the hydroxyl radical nor 8-hydroxydeoxyguanosine is formed by the reduction of hexavalent chromium, or that one or both of these is formed and then effectively removed by oxygen free radical scavengers or 8-hydroxydeoxyguanosine repair enzymes. Since increased exposure to hexavalent chromium did not result in increased 8-hydroxydeoxyguanosine levels, it is unlikely that hexavalent chromium induces lung cancer through 8-hydroxydeoxyguanosine formation.     

An analysis of chromium,copper, and zinc in organs of a chromate worker

Summary The content of chromium, copper, and zinc and the valency of chromium were measured in organs of a chromate worker who had been exposed to a considerable amount of hexavalent chromium for 30 years and died of maxillary and lung cancer 10 years after his retirement. The chromium in the lung of the worker averaged 3,555 ppb on a wet tissue weight basis, while those in the lung of five controls were 86.0–399 ppb. Organs other than the lung of the worker also had more chromium than those of the controls. The amounts of copper and zinc did not vary as widely as did chromium. The ratio of hexavalent chromium to total chromium was 29.3% in the lung of the worker and 12.9 to 38.7% in controls, and its ratio in the lung was lower than that in the other organs.     

Microscopic analysis of the chromium content in the chromium-induced malignant and premalignant bronchial lesions of the rat

OBJECTIVE: Our previous studies demonstrated that the frequency of gene instability in lung cancer of chromate workers was very high, but the frequencies of the p53 and ras gene mutations were low. To clarify the carcinogenesis of chromate in the lung, we established a chromate-induced cancer model in the rat proximal airway and examined the relationship between chromium accumulations and the chromium-induced cancer and premalignant bronchial lesions of the rat. METHODS: Fifteen male, bred, 12-week-old Jcl-Wister rats were used. A pellet of strontium chromate were inserted into the bronchus of the rats. The rats were sacrificed 9 months after the pellet was inserted. We pathologically examined the region of the bronchi to which the pellet was attached. We quantified the amount of chromium accumulation in the bronchial lesions using a microscopic X-ray fluorescence analyzer. RESULTS: Of the 15 rats, 1 rat had a lesion of squamous cell carcinoma (SCC), 7 rats had carcinoma in situ (CIS) or dysplasia, 8 rats had squamous metaplasia, and 5 rats had goblet cell hyperplasia. The amounts of chromium accumulation in normal epithelium (n=24), goblet cell hyperplasia (n=14), squamous metaplasia (n=8), and dysplasia plus CIS plus SCC (n=9) were 500+/-1354, 713+/-1062, 941+/-1328, and 3511+/-4473 (mean+/-SD) counts/s/mA, respectively. The amount of chromium accumulation was significantly increased according to the progression of malignant change of the bronchial epithelium (Spearman's correlation coefficient by ranks, rs=0.454, P<0.01). CONCLUSIONS: The amount of chromium accumulation was significantly increased according to the progression of malignant change of the bronchial epithelium. Examining the genetic alterations of histologic changes in this model was helpful in elucidating the process of carcinogenesis of chromium in the lung.     

Distribution of 24 Elements in the Internal Organs of Normal Males and the Metallic Workers in Japan

Concentrations of 24 elements in the internal organs from 12 healthy males and from 7 metallic workers in Japan were recorded. Markedly high concentrations of chromium were found in the respiratory organs (e.g., hilar lymph node and lung) of chromium plating and chromate refining workers, as well as in spleen, liver, kidney, and heart High chromium concentrations were also found in one male who had terminated his employment 30 years prior to his death. In addition, high concentrations of nickel and tin were also found in the above-mentioned workers. Marked accumulations of titanium, the main element of paints, were found in the respiratory organs, spleen, liver, kidney, and heart of an airplane painter. The painter also had high concentrations of chromium, nickel, and cobalt in some of his organs. It was also noted that high concentrations of silicon, aluminum, and titanium—elements of rock—occurred in a stone mason.     

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.     

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.     

可溶性铬盐职业接触者DNA链断裂的研究

目的通过对职业接触可溶性铬盐人群外周血淋巴细胞DNA链断裂水平的研究,了解该生物指标在职业人群中分布的水平、特点及其影响因素,探讨其作为职业接触铬盐人群生物标志物的可行性,为职业接触铬盐劳动者生物监测及健康危险性评价提供理论依据。方法本研究利用横断面现场研究,对山东省济南市某铬盐生产企业进行了流行病学调查。接触组选择重铬酸钾制造业铬盐作业健康劳动者114名(男74名、女40名),对照组为无毒物接触史的健康农民30名(男22名、女8名),两组人群在年龄、性别和吸烟状况等方面相匹配。通过问卷调查了解研究对象的一般情况、职业暴露情况、饮酒吸烟情况、既往疾病史(用药史)、急性感染情况、个人防护情况等。利用单细胞凝胶电泳法,检测外周血淋巴细胞DNA链断裂水平,并通过计算加权分评价损伤程度;作业环境铬盐浓度的测定采用双滤膜个体采样器8 h工作日连续采样,滤膜铬盐含量采用火焰原子吸收分光光度法测定;红细胞中铬浓度测定采用石墨炉原子吸收分光光度法。用SPSS10.0统计软件进行多元回归分析。结果(1)职业接触可溶性铬盐劳动者外周血淋巴细胞DNA链断裂水平得分为54.52±23.51,高于对照组的24.70±11.84,有统计学意义(P<0.01)。(2)当空气中个体铬盐暴露浓度小于106.00μg/m3时,职业接触可溶性铬盐劳动者DNA链断裂水平,随个体铬盐暴露水平的增加而增加,并呈明显的剂量-反应关系。(3)相关分析结果表明:外周血淋巴细胞DNA链断裂水平与空气中个体铬盐暴露水平、红细胞中铬浓度水平均呈显著的正相关性(P<0.01)。(4)多元回归证实:在α=0.10水平上,吸烟剂量、空气中铬盐浓度、接触铬盐的年限对淋巴细胞DNA链断裂水平影响显著。结论DNA链断裂可以作为职业接触可溶性铬盐劳动者遗传损伤效应性生物标志物,可望用于职业接触可溶性铬盐劳动者生物监测及健康危险性的评价。     

Investigations on the quantitative determination of nickel and chromium in human lung tissue

Summary Nickel (Ni) and some of its relatively insoluble compounds as well as chromates may be able to induce cancer in the region of the lungs, as well as in the nose and paranasal sinuses after occupational exposure. Latency periods may amount to 20 years and more. The results of recent investigations have shown that these metals cumulate in the lung tissue after inhalation of relatively insoluble chromium and nickel compounds. The quantitative detection of these heavy metals in samples of pulmonary tissue hence permits the amount of past exposure to be estimated. To establish the normal values, samples of pulmonary tissue from 30 normal subjects were investigated for chromium and nickel content. The samples were taken from different segments and lobes of the lungs, taking topographical anatomical criteria into consideration. In addition, 15 persons who had formerly been exposed to nickel and/or chromium (11 nickel refinery workers, of whom 10 had died of lung cancer, 2 stainless steel welders, 1 foundry worker, 1 electrical technician) were also investigated. From the results of 495 tissue samples from the normal group, median chromium concentrations between 130 and 280 ng/g were calculated, with median nickel concentrations of 20–40 ng/g (wet weight). If these values are related to the nickel concentrations measured in refinery workers, values 112-5,860 times higher were found. The concentrations were about 500 times higher than normal for nickel, and about 60 times higher than normal for chromium in the stainless steel welders. For the foundry workers who died of lung cancer, chromium and nickel concentrations in the normal range were calculated, with the exception of the nickel concentrations in the upper and lower lobes of the right lung. The very high nickel concentrations found in the samples of lung tissue from former nickel refinery workers should be regarded as a guideline with regard to the appraisal of the causal relationship between lung cancer and occupational exposure to relatively insoluble nickel compounds. This result is also supported by epidemiological investigations on this subgroup and must thus be considered etiologically conclusive. For the welders, chromium and nickel concentrations were found that were markedly above normal, but as yet there is no epidemiologically reliable verification for the increased occurrence of malignancies in this occupational group. On the basis of present scientific knowledge, no indications were found of relevant chromium and/or nickel exposure of the lung tissue that might be able to induce lung cancer in either foundry workers or for electric technicians.Dedicated to Professor V. Becker on his 65th birthday     

One hundred years of chromium and cancer: a review of epidemiological evidence and selected case reports

The present review is motivated by the fact that 100 years have passed since the first cancer case in a chromium worker was reported in Scotland. Old and recent case reports and epidemiological studies among chromate workers are reviewed to elucidate the importance of valency states and water solubility of chromium compounds for carcinogenic potency. It is concluded that all chromium[VI] compounds should be considered carcinogenic among exposed populations, and that no evidence has been presented indicating that human exposure to chromium[III] is associated with increased cancer risk. Strong evidence has been presented that zinc chromate is a potent carcinogen and suggests that calcium chromate may be a potent carcinogen. Evidence also suggests that water-soluble chromates in general may be more potent carcinogens than those with low solubility. Primary and secondary prevention of chromate-related cancer and the success in preventive measures are briefly discussed, and recommendations for future research are made.     

Low-level hexavalent chromium exposure and rate of mortality among US chromate production employees

OBJECTIVE: Although numerous studies have reported an elevated lung cancer risk among chromium chemical production employees, few studies have focused on employees hired after major process changes and enhanced industrial hygiene controls were implemented. METHODS: This study examines the mortality experience of two post-change cohorts of chromate production employees constituting the current US chromium chemical industry. RESULTS: Mortality among chromium chemical workers generally was lower than expected on the basis of national and state-specific referent populations. Lung cancer mortality was 16% lower than expected, with only three lung cancer deaths (3.59 expected). CONCLUSION: The absence of an elevated lung cancer risk may be a favorable reflection of the post-change environment. However, longer follow-up allowing an appropriate latency for the entire cohort will be needed to confirm this conclusion.     

Interaction of smoking, uptake of polycyclic aromatic hydrocarbons, and cytochrome P450IA2 activity among foundry workers.

An increased lung cancer risk has been described among foundry workers. Polycyclic aromatic hydrocarbons (PAHs) and silica are possible aetiological factors. This study describes a urinary PAH metabolite, 1-hydroxypyrene (hpU), as well as the degree of cytochrome P450IA2 activity/induction as reflected by the urinary caffeine ratio (IA2) in 45 foundry workers and 52 controls; IA2 was defined as the ratio of paraxanthine 7-demethylation products to a paraxanthine 8-hydroxylation product (1,7-dimethyluric acid). Mean exposure concentrations for foundry workers were defined by breathing zone hygienic samples (respirable dust 1.2 to 3.52 mg/m3 (93 samples)) and as total PAH (0.46 micrograms/m3) and pyrene concentrations (0.28 micrograms/m3) (six samples). Non-smoking controls and foundry workers had similar IA2 ratios (5.63, 95% confidence interval (95% CI) 4.56-6.70 and 4.40, 95% CI 3.56-5.24). The same was true for smoking controls and foundry workers (9.10, 95% CI 8.00-10.20 and 8.69, 95% CI 7.37-10.01). Both smoking groups had raised IA2 ratios compared with non-smokers (p less than 0.01). Non-smoking controls and foundry workers had similar hpU concentrations (0.16, 95% CI 0.10-0.22 and 0.11, 95% CI 0.09-0.13 mumol/mol creatinine). Smoking foundry workers had raised hpU concentrations (0.42, 95% CI 0.25-0.59) compared with smoking controls (0.26, 95% CI 0.18-0.34) (p less than 0.01). A small subgroup of smoking foundry workers with the highest exposures to both silica and PAH also had the highest hpU concentrations (0.70, 95% CI - 0.07-1.47 mumol/mol creatinine) (p less than 0.04). Increased hpU concentrations in smoking foundry workers suggest a more than additive effect from smoking and foundry exposures resulting in increased PAH uptake. Increased P450IA2 enzyme activity was only found in smokers and no additional effect of foundry exposures was seen. These data suggest that smoking as well as work related PAH exposure may be casually related to increased risk of lung cancer in foundry workers.     

Interaction of smoking, uptake of polycyclic aromatic hydrocarbons, and cytochrome P450IA2 activity among foundry workers.

An increased lung cancer risk has been described among foundry workers. Polycyclic aromatic hydrocarbons (PAHs) and silica are possible aetiological factors. This study describes a urinary PAH metabolite, 1-hydroxypyrene (hpU), as well as the degree of cytochrome P450IA2 activity/induction as reflected by the urinary caffeine ratio (IA2) in 45 foundry workers and 52 controls; IA2 was defined as the ratio of paraxanthine 7-demethylation products to a paraxanthine 8-hydroxylation product (1,7-dimethyluric acid). Mean exposure concentrations for foundry workers were defined by breathing zone hygienic samples (respirable dust 1.2 to 3.52 mg/m3 (93 samples)) and as total PAH (0.46 micrograms/m3) and pyrene concentrations (0.28 micrograms/m3) (six samples). Non-smoking controls and foundry workers had similar IA2 ratios (5.63, 95% confidence interval (95% CI) 4.56-6.70 and 4.40, 95% CI 3.56-5.24). The same was true for smoking controls and foundry workers (9.10, 95% CI 8.00-10.20 and 8.69, 95% CI 7.37-10.01). Both smoking groups had raised IA2 ratios compared with non-smokers (p less than 0.01). Non-smoking controls and foundry workers had similar hpU concentrations (0.16, 95% CI 0.10-0.22 and 0.11, 95% CI 0.09-0.13 mumol/mol creatinine). Smoking foundry workers had raised hpU concentrations (0.42, 95% CI 0.25-0.59) compared with smoking controls (0.26, 95% CI 0.18-0.34) (p less than 0.01). A small subgroup of smoking foundry workers with the highest exposures to both silica and PAH also had the highest hpU concentrations (0.70, 95% CI - 0.07-1.47 mumol/mol creatinine) (p less than 0.04). Increased hpU concentrations in smoking foundry workers suggest a more than additive effect from smoking and foundry exposures resulting in increased PAH uptake. Increased P450IA2 enzyme activity was only found in smokers and no additional effect of foundry exposures was seen. These data suggest that smoking as well as work related PAH exposure may be casually related to increased risk of lung cancer in foundry workers.     

Surfactant protein B gene variations and susceptibility to lung cancer in chromate workers

BACKGROUND: Hexavalent chromium has been extensively investigated regarding its mutagenicity and carcinogenicity; however, its mechanism for initiating and enhancing the development of lung cancer is still obscure. Biomarkers of exposure, effect or susceptibility are required for risk assessment and for epidemiologic research studies especially in occupational settings. Since the surfactant protein system (SP) is very important for normal lung function and for mediating local airway conditions and in the clearance of the upper respiratory tract from the occupational and environmental dusts, we hypothesize that SP genes may represent good candidates to study susceptibility for lung cancer. METHODS: Using PCR genotyping methods with gel electrophoresis and confirmation of results with precise DNA fragment size measurement on microchip electrophoresis, we analyzed SP-B intron-4 polymorphism in 230 subjects who were classified into groups; chromate-related lung cancer, control chromate workers who had not developed lung cancer, control individuals with non chromate-related adenocarcinoma or squamous cell carcinoma of the lungs, or healthy Japanese control individuals. RESULTS: Our results indicated that the SP-B variants (deletion/insertion) were significantly overrepresented (61.3%) in the chromate-related lung cancer group than other groups (X2 = 47.6; DF = 4, P = 0.0001). There was a significant difference between the chromate lung cancer group and both of the control groups, healthy individuals and chromate workers who did not develop lung cancer, showing odds ratios (OR) with 95% confidence intervals (CI) of 21.9 (7.3-65.7) and 19.0 (3.78-95.4), respectively. Compared with 46 non chromate-related SCC of the lung, the SP-B variants were significantly overrepresented in the chromate-related SCC (18/28; 64.3%) than the non-chromate SCC (11/46; 23.9%) of the lung samples (X(2) = 10.27, P = 0.01), OR with 95% CI is 5.73 (2.05-16.01). CONCLUSION: These findings indicate a very strong association of the SP-B intron-4 variants with mechanisms that may enhance lung cancer susceptibility, especially in workers who are employed in chromate industry. Moreover, confirmation of such results may help to suggest adding the SP-B intron-4 typing to be one of the screening tests of the pre-placement medical examination to confirm that the worker has no variations of the SP-B gene before being engaged in a chromium-related industry, with the intention of providing proper medical counseling.