H. J. Raithel

Biologic monitoring of chromium and nickel among stainless steel welders using the manual metal arc method

SummaryForty manual metal arc welders welding stainless steel (SS) were monitored for 1–7 workdays measuring total chromium (Cr), water-soluble hexavalent CrVI, and nickel (Ni) in the working atmosphere, and Cr and Ni in blood and urine. The mean daily increase was 1.0 μg Cr/l in plasma and 5.6 μg Cr/g creatinine in urine. There were significant correlations between total Cr and CrVI in air and the total Cr in biologic fluids. This was not the case for the corresponding correlations for Ni. The observed correlations between urinary and plasma Cr levels may permit interchange of these body fluids for biologic monitoring at high exposures. The results indicate that urine sampled after work is a body fluid versatile for routine monitoring of Cr in SS welders. Smokers had higher levels of Cr in biologic fluids than did nonsmokers at equivalent levels of air CrVI. The results also indicate that filter masks provide better protection against uptake of Cr in the airways than air-stream helmets.

Evaluation and classification of high-resolution computed tomographic findings in patients with pneumoconiosis

The standard ILO classification for pneumoconiotic changes using conventional X-ray films has become well established. In recent years computed tomography has played an increasing role in occupational medicine and above all in the assessment of pneumoconiosis. Therefore a standardised method of classification for CT also seems necessary. A system of classification developed by occupational hygienists and radiologists allows a detailed description of parenchymal and pleural changes and the use of 28 additional symbols. Furthermore, special diagnoses relevant to occupational medicine and additional comments can be made. The classification system was tested in practice in the research project “Early diagnosis of asbestos-related diseases” (Frühdiagnostik asbestverursachter Erkrankungen). It was shown to be both practicable and easily reproducible, intra-individually and interindividually.

Biomonitoring of nickel and chromium in human pulmonary tissue

SummaryNickel (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.

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

SummaryNickel (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.

Acute fatal selenium poisoning

Neutralizing selenic acid with caustic soda caused a hyperintensive exothermic reaction, with about 450 1 of the reaction mixture erupting in a factory hall. A 44-year-old industrial worker was fatally intoxicated, suffering from second-degree skin burns, necrosis of oral mucous membranes and hemorrhagic lung edema. He died 90 min later. Analysis of body fluids and tissue samples showed high selenium concentrations in blood serum, urine, stomach content and lungs. The analytical results are discussed in comparison with normal selenium levels of non-exposed groups.

Cancer mortality in a surveillance cohort of German males formerly exposed to asbestos.

The objective of this analysis was the estimation of the cancer risks of asbestos and asbestosis in a surveillance cohort of high-exposed German workers. A group of 576 asbestos workers was selected for high-resolution computer tomography of the chest in 1993-1997. A mortality follow-up was conducted through 2007. Standardised mortality ratios (SMRs) were calculated and Poisson regression was performed to assess mesothelioma risks. A high risk was observed for pleural mesothelioma (SMR 28.10, 95% CI 15.73-46.36) that decreased after cessation of exposure (RR 0.1; 95% CI 0.0-0.6 for > or =30 vs. <30 years after last exposure). Asbestosis was a significant risk factor for mesothelioma (RR 6.0, 95% CI 2.4-14.7). Mesothelioma mortality was still in excess in former asbestos workers although decreasing after cessation of exposure. Fibrosis was associated with subsequent malignancy.

Investigations of thallium-exposed workers in cement factories

SummaryThallium and its compounds have a high toxic potency. For the production of particularly resistant sorts of cement, additives containing thallium, among other things, are employed. In conformity with our present toxicological knowledge, the determination of the concentration of thallium in the urine must be considered a suitable parameter for the assessment of the presence of thallium in the body. Occupational-medical preventive examinations were carried out in a total of 128 male employees from all areas of production in three cement factories. An exposure of these employees to thallium was objectified by analyses of the roasted pyrites employed and the dust from the electric filter. The study included the questioning of the employees with respect to their previous history of health, and also a physical examination aimed at detecting clinical symptoms of a possible effect of thallium. The analysis of thallium was carried out in samples of “spontaneous” urine. The analytical method employed was flameless atomic absorption spectroscopy (carbon-rod atomizer).In part, the group of persons investigated revealed excretions of thallium slightly or moderately above the normal level (range: < 0.3-6.3 μg/g creatinine). As the upper normal limit of thallium excretion, we computed a value of 1.1 μg/g creatinine.In no case, however, did the case history data or the findings of the physical examination reveal any indication of the symptoms characteristic of thallium poisoning.

Analyses of chromium and nickel in human pulmonary tissue

SummaryAfter 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.

Changes in low molecular weight DNA fragmentation in white blood cells of workers highly exposed to asbestos.

Objective: The aim of this study was to determine low molecular weight (LMW)-DNA fragmentation changes after white blood cell (WBC) incubation in lysis buffer followed by constant-field gel electrophoresis (CFGE). WBCs were isolated from blood samples of workers highly exposed to asbestos fibres at the workplace in Germany, and were compared with those from healthy adults. This study was conducted parallel to the study presented in our preceding paper (Marczynski et al. 2000b) in which we described significant increases in the levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG) adducts in the DNA of white blood cells from the same highly exposed workers relative to the levels found in the control group in all three study years (1994 to 1997). Method: We found that 15-h incubation in lysis buffer of WBCs embedded in agarose-plugs from healthy control donors with 2% SDS, proteinase K and Na2-EDTA at 42 °C followed by 0.5 h at 4 °C produced a characteristic DNA fragmentation pattern below 23 kbp using CFGE. Results: In the 1st year of the study (1994–1995) changes were found in LMW-DNA fragmentation in 54.8% of the asbestos workers studied, compared with the DNA fragmentation pattern of controls. Interestingly, in the 2nd year of the study (1995–1996) changes in DNA fragmentation were found in only 39.9% of exposed subjects. In the 3rd year of the study (1996–1997) the highest number of workers exposed to asbestos (67.3%) with changes in the LMW-DNA fragmentation pattern was found. The Chi-square test for each year of the study revealed significant changes (P < 0.001). These changes may be due to the presence of hydrogen peroxide (H2O2), as has been shown in vitro. It is likely that a Fenton reaction involving the heterolytic reduction of H2O2 by traces of reduced transition metals such as Fe2+ and Cu+ is involved in the fragmentation of DNA. No difference was found in the changes in DNA fragmentation between asbestos-exposed subjects with and without benign asbestos-associated diseases (asbestosis, asbestos-associated pleural plaques). Significant correlations were not found after analysis of the changes in DNA fragmentation in relation to different possible occupational and non-occupational confounding factors, such as the duration of asbestos exposure, the latency period, estimated cumulative fibrous dust dose (“fibre-years”), and non-occupational confounding factors, such as age, smoking status, acute febrile infections, the intake of medicines, aspirin, Ca2+, Mg2+ and/or hormones, the intake of vitamins, and cases of cancer. Conclusions: Our data confirm that oxidative stress occurs in the WBCs of workers highly exposed to asbestos fibres, thus supporting the hypothesis that asbestos fibres damage cells through an oxidative mechanism. Oxidative stress and oxidative DNA damage may be induced by long-term exposure to asbestos. The new insights into the oxidative effects of asbestos fibres are of great importance because they provide a way forward for new preventive strategies. Preventive and therapeutic approaches using antioxidants should be taken into consideration.

Increased content of chromium and nickel in lung tissues from patients with bronchial carcinoma.

Epidemiological studies have shown that occupational exposure to certain chromium and nickel compounds is followed by an increased lung cancer incidence. However, few data exist on the content of these metals in lung cancer patients in general. In the present study, central and peripheral lung tissue, bronchial tissue and hilar lymph nodes were collected from 20 patients with bronchial carcinoma and 21 control individuals, and the tissue concentration of chromium and nickel was measured by use of atomic absorption analysis. Increased levels of both metals were found in cancer patients as compared to controls. Lung tissue concentration of chromium was two-fold increased, while the bronchial wall content of nickel was three times the level in control individuals. Smokers showed a dose-related increase in the deposition of both chromium and nickel. Furthermore, in cancer patients an inverse relationship between smoking and the tissue level of chromium in regional lymph nodes was found, possibly indicating a depressive effect on pulmonary clearance mechanisms. Our results emphasize the possible role of small amounts of chromium and nickel as agents in bronchial carcinogenesis, unrelated to occupation and probably related to tobacco smoking.