Biomonitoring of nickel and chromium in human pulmonary tissue

Nickel (Ni) and chromium (Cr) and some of its compounds may be able to induce cancer in the lungs as well as in the nose and paranasal sinuses after occupational exposure. Latency periods amount to 20 years and more. Therefore objective exposure data are not available in the most cases and expert evaluation of the causal connection is often difficult. Recent investigations have shown, that Ni and Cr can cumulate in human lung tissue after occupational exposure. For the evaluation of normal Ni- and Cr-values a total of 495 human lung tissue samples of 30 occupationally non-exposed persons were analysed by AAS including ZEEMAN-compensation after wet oxidative digestion. Additional samples of 10 deceased persons who have been occupationally exposed to nickel in previous times by nickel-refining and welding, especially flame spraying have been investigated. The median Ni- and Cr- concentrations in the lungs of the non-exposed persons ranged between 20–40 resp. 133–277 ng/g (wet weight). In nickel refinery workers Ni- concentrations were found which exceeded the normal range about 1,000. In welders, especially flame sprayers, also values more than 100 times higher could be analysed for Ni and Cr. Partially these concentrations were found years after the end of the inhalative exposure.     

Analyses of chromium and nickel in human pulmonary tissue

After inhalative occupational exposure to certain compounds containing nickel and chromium (mostly over many years), an accumulation of these metals may occur in the lung tissue. This is of particular importance, both from a toxicological point of view and with regard to expert reports, since certain nickel and chromium compounds may induce lung cancers. In the context of this study, samples of pulmonary tissue from 34 deceased persons from the Bergen area (Norway) were analysed by atomic absorption spectrometry with regard to their content of chromium and nickel. The deceased comprised 21 men and 13 women. In 15 cases, death resulted from lung cancer; in the other 19 deceased, there was no indication of a malignant disease of the airways. The concentrations of nickel found in the lung tissue do not differ between patients with lung cancer and patients with healthy lungs. On the other hand, the concentration of chromium in the pulmonary tissue in the patients who had died of lung cancer and who had all been inhalative smokers, are higher (statistically significant) than in the nonsmokers or in those with healthy lungs. An accumulation of these two metals in the tumor matrix could not be detected. Both the average nickel and the average chromium concentrations were higher in the persons who had probably been exposed occupationally. Considering the present state of scientific knowledge, the aspects relevant to expert reports which result from the analyses of metals in the pulmonary tissue are discussed.     

Can lung cancer risk among nickel refinery workers be explained by occupational exposures other than nickel?

BACKGROUND: Exposures in nickel refineries represent complex chemical mixtures, but only the effect of nickel has been evaluated quantitatively in epidemiologic studies of nickel workers. METHODS: For a Norwegian refinery, time- and department-specific exposure estimates were developed for arsenic, sulfuric acid mists, and cobalt in air on the basis of personal measurements and chemical data on raw materials and process intermediates. Exposure to asbestos, as well as employment in high-risk occupations outside the refinery, were assessed. We conducted a case-control study nested in a cohort of refinery workers, with 213 cases (diagnosed 1952-1995) and 525 age-matched controls. We analyzed lung cancer risk, adjusted for smoking, by cumulative exposure and duration of work. RESULTS: There was a substantial association between cumulative exposure to water-soluble nickel and lung cancer risk. Weaker effects were suggested for exposure to arsenic at the refinery and for occupational exposures outside the refinery for 15 years or more. No detectable excess risk was found for refinery exposure to asbestos or sulfuric acid mists, and no dose-related increase in risk was seen from cobalt. CONCLUSIONS: Exposure to water-soluble nickel remained the most likely explanation for the excess lung cancer risk in the cohort. Other occupational exposures did not confound the strong dose-related effect of nickel to any appreciable degree.     

Assessment of risk of lung cancer for welders

Certain welding fumes contain significant amounts of chromium, manganese, and nickel, and trace amounts of arsenic and lead. These metals exhibit mutagenicity in one or more in vitro bioassays, and several are strongly suspected human carcinogens, albeit in unknown forms. It might, therefore, be expected that welders experience an excess risk of respiratory tract cancer because of their occupation. A survey of the world literature has disclosed 22 epidemiological studies of cancer incidence among welders, 16 of which yield a total of 586 cases of lung cancer observed, based on approximately 600,000 man-years at risk; a risk ratio of less than unity was excluded within 95% confidence limits for 5 of these studies. A risk ratio of 1.3 was not excluded in any study. Although there may be many possible origins to the excess risk, if welders of stainless steels suffer an "equivalent lung cancer risk" to that of chromate workers because of their equivalent chromium (VI) exposure, then a resulting three-fold risk ratio for 10% of all welders engaged in stainless steel welding would account for the total over-incidence experienced by the entire occupational group.     

Determination of nickel in lung specimens of thirty-nine autopsied nickel workers

Summary Lung specimens from 39 nickel refinery workers autopsied during the period from 1978 to 1984 were analyzed for nickel. Fifteen of the workers were employed in the Roasting and Smelting Department, where exposure to nickel was predominantly in the form of nickel-copper oxides, Ni₃S₂ and metallic dust. The remaining 24 men worked in the Electrolysis Department. Exposure in this group was considered to be mostly to the water-soluble compounds, NiSO₄ and NiCl₂, but also to a lesser degree to water-insoluble nickel compounds such as nickel-copper oxides and sulphides. The arithmetic mean ± SD for nickel concentration in lung tissues expressed in gg^–1 dry wt for the 39 workers was 150 ± 280. In the workers employed in the Roasting and Smelting Department, the average nickel concentration was 330 ± 380; for those who worked in the Electrolysis Department it was 34 ± 48. Lung tissue from 16 autopsied persons not connected with the refinery had an average nickel concentration of 0.76 ± 0.39. Statistical analysis based on log-normal distributions of the measured nickel concentrations allowed three major conclusions to be formulated: (1) nickel refinery workers exhibit elevated nickel levels in lung tissues at autopsy; (2) workers of the Electrolysis Department and the Roasting Smelting Department constitute distinct groups with respect to the accumulation of nickel in lung tissue; (3) workers who were diagnosed to have lung cancer had the same lung nickel concentrations at autopsy as those who died of other causes.     

Analyses of chromium and nickel in human pulmonary tissue

Summary After inhalative occupational exposure to certain compounds containing nickel and chromium (mostly over many years), an accumulation of these metals may occur in the lung tissue. This is of particular importance, both from a toxicological point of view and with regard to expert reports, since certain nickel and chromium compounds may induce lung cancers. In the context of this study, samples of pulmonary tissue from 34 deceased persons from the Bergen area (Norway) were analysed by atomic absorption spectrometry with regard to their content of chromium and nickel. The deceased comprised 21 men and 13 women. In 15 cases, death resulted from lung cancer; in the other 19 deceased, there was no indication of a malignant disease of the airways. The concentrations of nickel found in the lung tissue do not differ between patients with lung cancer and patients with healthy lungs. On the other hand, the concentration of chromium in the pulmonary tissue in the patients who had died of lung cancer and who had all been inhalative smokers, are higher (statistically significant) than in the nonsmokers or in those with healthy lungs. An accumulation of these two metals in the tumor matrix could not be detected. Both the average nickel and the average chromium concentrations were higher in the persons who had probably been exposed occupationally. Considering the present state of scientific knowledge, the aspects relevant to expert reports which result from the analyses of metals in the pulmonary tissue are discussed.     

Update of cancer incidence among workers at a copper/nickel smelter and nickel refinery

Objectives: To assess cancer risk among nickel-exposed workers. Methods: We updated cancer incidence among 1388 workers employed for at least 3 months at a copper/nickel smelter and nickel refinery in Harjavalta, Finland. There were 1155 workers exposed to nickel during the period 1960–1985 in the smelter (566 workers), repair shop (239 workers), or refinery (418 workers). Cancer incidence was followed through the files of the Finnish Cancer Registry up to 31 December 1995. For overall cancer and for a priori selected specific cancer types the ratio of observed to expected numbers of cases was computed as a standardized incidence ratio (SIR), controlled for age, gender, and calendar period and using the region-specific rates as a reference. Results: The overall cancer incidence among both nickel-exposed and unexposed subcohorts was at the expected level. A small increase in lung cancer incidence, which reached statistical significance among workers with a latency exceeding 20 years, was observed among the smelter workers exposed to insoluble nickel compounds. Among workers in the refinery, who were exposed primarily to nickel sulfate at levels below 0.5 mg/m³ as well as to low concentrations of other nickel compounds, there was an increased risk for nasal cancer (SIR 41.1, 95% CI 4.97–148), positively associated with latency and duration of employment, and an excess risk for stomach (SIR 4.98, 95% CI 1.62–11.6) and lung (SIR 2.61, 95% CI 0.96–5.67) cancers. Conclusions: Since elevated nasal and lung cancer risks were confined to the refinery, where the primary exposure was to nickel sulfate, it is likely that nickel sulfate is mainly responsible for the elevated respiratory cancer risk. We cannot rule out whether the excess stomach cancer risk is a chance finding, or related to the working environment. Received: 11 September 1997 / Accepted: 17 October 1997     

A historical prospective study of European stainless steel, mild steel, and shipyard welders.

A multicentre cohort of 11,092 male welders from 135 companies located in nine European countries has been assembled with the aim of investigating the relation of potential cancer risk, lung cancer in particular, with occupational exposure. The observation period and the criteria for inclusion of welders varied from country to country. Follow up was successful for 96.9% of the cohort and observed numbers of deaths (and for some countries incident cancer cases) were compared with expected numbers calculated from national reference rates. Mortality and cancer incidence ratios were analysed by cause category, time since first exposure, duration of employment, and estimated cumulative dose to total fumes, chromium (Cr), Cr VI, and nickel (Ni). Overall a statistically significant excess was reported for mortality from lung cancer (116 observed v 86.81 expected deaths, SMR = 134). When analysed by type of welding an increasing pattern with time since first exposure was present for both mild steel and stainless steel welders, which was more noticeable for the subcohort of predominantly stainless steel welders. No clear relation was apparent between mortality from lung cancer and duration of exposure to or estimated cumulative dose of Ni or Cr. Whereas the patterns of lung cancer mortality in these results suggest that the risk of lung cancer is higher for stainless steel than mild steel welders the different level of risk for these two categories of welding exposure cannot be quantified with precision. The report of five deaths from pleural mesothelioma unrelated to the type of welding draws attention to the risk of exposure to asbestos in welding activities.     

A historical prospective study of European stainless steel, mild steel, and shipyard welders

A multicentre cohort of 11,092 male welders from 135 companies located in nine European countries has been assembled with the aim of investigating the relation of potential cancer risk, lung cancer in particular, with occupational exposure. The observation period and the criteria for inclusion of welders varied from country to country. Follow up was successful for 96.9% of the cohort and observed numbers of deaths (and for some countries incident cancer cases) were compared with expected numbers calculated from national reference rates. Mortality and cancer incidence ratios were analysed by cause category, time since first exposure, duration of employment, and estimated cumulative dose to total fumes, chromium (Cr), Cr VI, and nickel (Ni). Overall a statistically significant excess was reported for mortality from lung cancer (116 observed v 86.81 expected deaths, SMR = 134). When analysed by type of welding an increasing pattern with time since first exposure was present for both mild steel and stainless steel welders, which was more noticeable for the subcohort of predominantly stainless steel welders. No clear relation was apparent between mortality from lung cancer and duration of exposure to or estimated cumulative dose of Ni or Cr. Whereas the patterns of lung cancer mortality in these results suggest that the risk of lung cancer is higher for stainless steel than mild steel welders the different level of risk for these two categories of welding exposure cannot be quantified with precision. The report of five deaths from pleural mesothelioma unrelated to the type of welding draws attention to the risk of exposure to asbestos in welding activities.     

Effects on the nervous system in different groups of workers exposed to aluminium

OBJECTIVE—To investigate possible neurotoxic effects in groups of aluminium pot room and foundry workers, aluminium welders, and a small group of workers exposed to aluminium in the production of flake powder.
METHODS—Exposure to aluminium was evaluated with aluminium concentrations in blood and urine as well as a questionnaire. The groups exposed to aluminium were compared with a group of mild steel welders. Neurotoxic effects were studied with mood and symptom questionnaires and several psychological and neurophysiological tests.
RESULTS—The pot room and foundry workers showed very low aluminium uptake as their aluminium concentrations in blood and urine were close to normal, and no effects on the nervous system were detected. The group of workers exposed to flake powder had high concentrations of aluminium in blood and urine, even higher than those of the aluminium welders. However, aluminium could not be shown to affect the functioning of the nervous system in flake powder producers. Although significant effects could not be shown in the present analysis of the data on welders, the performance of the welders exposed to high concentrations of aluminium was affected according to the analyses in the original paper from this group.
CONCLUSIONS—For the pot room and foundry workers no effects related to the exposure to aluminium could be found. For the group of flake powder producers exposed for a short term no effects on the nervous systems were evident despite high levels of exposure. Due to the high concentrations of aluminium in the biological samples of this group, measures to reduce the exposure to aluminium are recommended, as effects on the central nervous system might develop after protracted exposures. However, this assumption needs to be verified in further studies.


Keywords: aluminium; workers; nervous system     

Lung cancer in mild steel welders

To investigate lung cancer risk, the authors conducted a historical cohort mortality study of 4,459 mild steel welders who had been employed at three midwestern plants which manufactured heavy equipment. Follow-up began in the mid-1950s and extended through 1988. All welders had at least 2 years welding experience (average duration, 8.5 years). This cohort had no occupational exposure to asbestos or stainless steel fumes (containing nickel and chromium), two potential confounders in previous welders studies. A comparison population of 4,286 nonwelders, all with at least 2 years employment at the same plants, was also studied. Nonwelders had never been welders and were allowed to have no more than 90 days employment as a painter, foundryman, or machinist. Sampling data collected from 1974-1987 indicated that welders were exposed to 6-7 mg/m3 of total particulate and 3-4 mg/m3 of iron oxide, while nonwelders had negligible exposures to welding fumes. When compared with the United States population, both welders and nonwelders had elevated rates for lung cancer (standardized mortality ratios (SMRs): welders, SMR = 1.07; nonwelders, SMR = 1.17), but neither SMR was significantly elevated. Limited smoking data based on a 1985 survey indicated that both welders and nonwelders smoked more than the United States population, possibly accounting for part of their elevated lung cancer rates. There was no trend of increased risk for welders with increased duration of exposure. The only other cause of death significantly elevated was emphysema among welders. Nonmalignant respiratory disease was not elevated for welders (SMR = 0.96). When welders were compared with nonwelders directly for lung cancer, the rate ratio was 0.90.     

Polycyclic aromatic hydrocarbons (PAHs): a possible cause of lung cancer mortality among nickel/copper smelter and refinery workers.

A retrospective industrial hygiene investigation was undertaken to explain the cause of a statistically significant excess lung cancer mortality observed in a subset of a large cohort of nickel workers involved in mining, smelting, and refining of nickel and copper in Ontario. The focus of this paper is to demonstrate how an industrial hygiene follow-up assessment of an epidemiologic finding can help to identify a likely cause. Polycyclic aromatic hydrocarbons (PAHs) alone or in association with particulate and gaseous contaminants (e.g., SO2) were likely the causative agents of the excess lung cancer observed among the lead welders, cranemen, and arc furnace workers of the copper refinery.     

Lung-retained contaminants,urinary chromium and nickel among stainless steel welders

Summary The magnetic method of measuring the amount of lung retained contaminants as well as urinary chromium and nickel determinations have been performed among 83 stainless steel (SS) welders who have used matural metal arc (MMA) and tungsten inert gas (TIG) welding techniques. The welders were divided into four groups according to the time percentage used for MMA welding. Only exposure to MMA/SS welding fumes resulted in clearly elevated chromium concentrations in the urine, the correlation coefficient between the values of urinary chromium and MMA/SS percentage being very significant (P < 0.001). Among the smokers the urinary chromium values were increased (P < 0.05) perhaps owing to contaminated cigarettes. In many workplaces the urinary chromium values of several welders exceeded the value of 30 g/l which is the recommended reference value in Finland. Owing to the solubility properties of nickel compounds in SS welding fumes urinary nickel concentrations were only slightly elevated among MMA/SS welders, and therefore, the urinary nickel determinations do not reflect the level of exposure to nickel compounds. The measured average remanent magnetic field of the chest area correlated well (P < 0.01) with the use of the MMA technique. A very significant correlation (P < 0.001) existed between the average remanent magnetic fields of the chest and the urinary chromium values of MMA/SS welders.     

A mortality study among mild steel and stainless steel welders.

A mortality study was carried out in conjunction with the European mortality study among welders coordinated by the International Agency for Research on Cancer (IARC). The study was aimed at assessing risks for lung cancer in relation to exposure to asbestos, welding fumes containing chromium and nickel, and tobacco smoke. The study included a cohort of 2721 welders and an internal comparison group of 6683 manual workers employed in 13 factories in France. The mortality of the two cohorts was studied from 1975 to 1988 by the historical prospective method. Job histories of welders were traced including welding processes used, metals welded, and proportion of worktime spent in welding. Data on smoking habits were collected from medical records. The observed number of deaths were compared with those expected (standardised mortality ratio (SMR)) based on national rates with adjustments for age, sex, and calendar time. The smoking habits of 87% of the whole study population were known. The distribution of welders and controls according to smoking was not statistically different. The overall mortality was slightly higher for welders (SMR = 1.02, 95% confidence interval (95% CI) 0.89-1.18) than for controls (SMR = 0.91, 95% CI 0.84-0.99). For lung cancer, the SMR was 1.24 (95% CI 0.75-1.94) for welders, whereas the corresponding value was lower for controls (SMR = 0.94, 95% CI 0.68-1.26). The SMR for lung cancer was 1.59 among non-shipyard mild steel welders (95% CI 0.73-3.02). This contrasted with the results for all stainless steel welders (SMR = 0.92, 95% CI 0.19-2.69), and for stainless steel welders predominantly exposed to chromium VI (SMR = 1.03, 95% CI 0.12-3.71). Moreover, SMRs for lung cancer for mild steel welders tended to increase with duration of exposure and time since first exposure, leading to significant excesses for duration > or = 20 years and latency > or = 20 years. Such a pattern was not found for stainless steel welders.     

上海市宝山区焊接作业场所中电焊烟尘和锰及其无机化合物浓度调查

目的了解上海市宝山区焊接作业场所中电焊烟尘、锰及其无机化合物浓度情况。方法以个体采样方法采集电焊烟尘和锰及其无机化合物,分别采用滤膜称重法和火焰原子吸收光谱法分别进行检测。结果分别对91名焊工和47名焊工进行电焊烟尘和锰及其无机化合物个体采样,结果 28人(30.8%)电焊烟尘时间加权平均(TWA)浓度超过国家职业接触限值,14人(29.8%)锰及其化合物浓度超过国家职业接触限值。CO2气保焊组电焊烟尘TWA均值为5.22 mg/m3,是其他焊接组TWA均值的2.8倍,锰及其无机化合物TWA均值为0.221 mg/m3,是其他焊接组TWA均值的2.7倍。结论 CO2气保焊岗位电焊烟尘、锰及其无机化合物职业危害都较严重。工厂企业应加强职业卫生管理,改善工作环境,为焊工配备有效的个人防护用品,以保障工人身体健康。     

Relation between various chromium compounds and some other elements in fumes from manual metal arc stainless steel welding.

For the years 1987-1990 160 individual samples of manual metal arc stainless steel (MMA/SS) welding fumes from the breathing zone of welders in four industrial plants were collected. Concentrations of soluble and insoluble chromium (Cr) III and Cr VI compounds as well as of some other welding fume elements (Fe, Mn, Ni, F) were determined. Concentration of welding fumes in the breathing zone ranged from 0.2 to 23.4 mg/m3. Total Cr amounted to 0.005-0.991 mg/m3 (including 0.005-0.842 mg/m3 Cr VI). Total Cr content of fumes varied from 0.1 to 7.4%. The distribution of particular Cr compounds was: 52.6% soluble Cr (including 50.7% Cr VI), 65.5% total Cr VI, and 11.4% insoluble Cr VI. The results obtained indicate that MMA/SS welding is a process that could be highly hazardous to human health. Evaluation of occupational exposure has shown that MMA/SS welders may exceed the admissible concentrations of soluble and insoluble Cr VI forms as well as of Mn and Ni. In the plants investigated the sum of the ratios of concentrations of particular welding fumes in the breathing zone of welders exceeded corresponding maximum allowable concentration values by 24 times (including 17 times for total Cr VI). Due to the variety and changeability of particular parameters occurring in the working environment, the composition of MMA/SS welding fumes (in the welder's breathing zone) is so variable that it is not possible to assess the exposure by means of one universal exposure indicator (maximum additive hygienic limit value). The evaluation should be based on the results of measurements of concentrations of particular elements in welding fumes.     

美国EPA吸入风险评估模型在某电镀企业职业危害风险评估中的应用

[目的]探讨定量评估方法在职业危害风险评估中的实际应用价值。[方法]对某电镀生产企业,依据美国环境保护署（EPA）《人体健康风险评估手册F部分：吸入风险评估补充指南》的基本原理,开展现场调查和危害识别、暴露期与暴露方式评估、暴露评估、职业病危害致癌与非致癌性风险评估。[结果]该企业职业危害暴露途径以呼吸道暴露为主,暴露期符合亚慢性暴露特征。经检测除油岗位盐酸、预镀铜岗位氰化物、镀铬岗位三氧化铬的8 h时间加权平均浓度分别为5.2-5.8、0.16-0.19、0.018-0.023 mg/m^3。非致癌风险评估显示,除油、预镀铜、镀铬岗位的危害商数分别为75、61、360,均〉1,健康风险较大。致癌风险评估显示,镀镍岗位接触可溶性镍化合物、镀铬岗位接触三氧化铬的致癌风险（Risk）分别为1.0×10^-4、2.4×10^-3,均〉1×10^-6,具有致癌风险。[结论]镀镍岗位接触可溶性镍化合物、镀铬岗位接触三氧化铬的浓度均达标,但仍具有致肺癌风险。针对无法查询到相应参考值数据（参考浓度或吸入单元风险）的危害因素,不能直接应用该模型开展风险评估。     

Occupational risk factors of lung cancer: a hospital based case-control study

OBJECTIVES: To investigate the relation between lung cancer and exposure to occupational carcinogens in a highly industrialised region in western Europe. METHODS: In a case-control study 478 cases and 536 controls, recruited from 10 hospitals in the Antwerp region, were interviewed. Cases were male patients with histologically confirmed lung cancer; controls were male patients without cancer or primary lung diseases. Data were collected by questionnaires to obtain information on occupations, exposures, and smoking history. Job titles were coded with the Office of Populations, Censuses and Surveys industrial classification. Exposure was assessed by self report and by job-task exposure matrix. Exposure odds ratios were calculated with logistic regression analysis adjusted for age, smoking history, and marital and socio-economic status. RESULTS: A job history in the categories manufacturing of transport equipment other than automobiles (for example, shipyard workers), transport support services (for example, dockers), and manufacturing of metal goods (for example, welders) was significantly associated with lung cancer (odds ratios (ORs) 2.3, 1.6, and 1.6 respectively). These associations were independent of smoking, education, civil, and economic status. Self reported exposure to potential carcinogens did not show significant associations with lung cancer, probably due to nondifferential misclassification. When assessed by job-task exposure matrix, exposure to molybdenum, mineral oils, and chromium were significantly associated with lung cancer. A strong association existed between smoking and lung cancer: OR of ex- smokers 4.2, OR of current smokers 14.5 v non-smokers. However, smoking did not confound the relation between occupational exposure and lung cancer. CONCLUSIONS: The study has shown a significant excess risk of lung cancer among workers in manufacturing of metal goods, manufacturing of transport equipment (other than automobiles), and transport support services. Assessment of exposure to specific carcinogens resulted in significant associations of chromium, mineral oils, and molybdenum with lung cancer. This study is, to our knowledge, the first study reporting a significant association between occupational exposure to molybdenum and lung cancer.       

Metal concentrations in lung tissue of subjects suffering from lung cancer

Summary Concentrations of nine metals (Fe, Ca, Mg, Zn, Cu, Co, Ni, Pb and Cr) concentrations in lung tissues from 224 lung cancer cases were compared with those in other cases to achieve an understanding of their contribution to the development of lung cancer and the varieties after the development of cancer. Comparisons of metal concentrations in each cell type of lung cancer were also performed. All cases were collected from routine autopsies in Tokyo and Saitama, Japan. The copper concentration in tissue from lung cancers was significantly higher than that in other specimens, although calcium, magnesium, zinc and cobalt concentrations in lung cancers were significantly lower than those in other cases. There were no significant differences in the 99% intervals (excluding extremely high values for occupationally exposed cases) for chromium, nickel and lead concentrations between lung cancers and other cases, although these values were lower in lung cancers. However, in comparisons of men only, the chromium concentration, the degree of lung contamination and the severity of pulmonary emphysema in lung cancer cases were significantly higher than those in other specimens. Moreover, percentages of lung cancer in men at each degree of contamination and each severity of emphysema increased with increasing grades. Thus, this finding could be evidence that the exposure to contaminants other than chromium and nickel in the air had affected the development of lung cancer, except for occupationally exposed individuals. Therefore, almost all chromium and nickel in lung tissue might not deposit in carcinogenic forms such as hexavalent chromium or nickel subsulfide. Comparison of the characteristics in each cell type of lung cancer revealed that calcium and chromium concentrations in lung tissue (not including tumor) or squamous cell carcinomas were higher than those in the other cell types. In small cell carcinomas, calcium magnesium and zinc concentrations were low.     

Exposure to nickel compounds and smoking in relation to incidence of lung and nasal cancer among nickel refinery workers.

OBJECTIVES: To investigate the relation between occupational hazards among nickel refinery workers and their exposure to different forms of nickel over time and the interaction between smoking and total exposure to nickel. METHODS: The cohort consisted of 379 workers with first employment 1916-40 and at least three years of employment and 4385 workers with at least one year of employment 1946-83. Data on smoking (ever or never) were available for almost 95% of the cohort. Two analyses were used, indirect standardisation from observed and expected numbers and Poisson regression. RESULTS: During the follow up 1953-93, 203 new cases of lung cancer were observed v 68 expected (standardised incidence ratio (SIR) 3.0, 95% confidence interval (95% CI) 2.6-3.4) and 32 cases of nasal cancer were observed v 1.8 expected (SIR 18.0, 95% CI 12-25). The Poisson regression analysis showed an excess risk of lung cancer in association with exposure to soluble forms of nickel, with a threefold increase in relative risk (RR) (P < 0.001) and a multiplicative effect of smoking and exposure to nickel. The RRs were 1.1 (95% CI 0.2-5.1) for exposed workers who had never smoked and 5.1 (95% CI 1.3-20.5) for exposed workers who smoked. CONCLUSION: It is not possible to state with certainty which specific nickel compounds are carcinogenic, but a significant excess risk was found for workers exposed to soluble nickel alone or in combination with other forms of nickel. The present study suggests a multiplicative effect of smoking and nickel exposure.