Bronchial carcinoma mortality in the German chromate-producing industry: the effects of process modification.

This study updates a 1982 report on mortality at two German chromate-producing factories. The main objective of the study was to establish whether the change-over to a production process using lime-free conversion of chromite ore, thus eliminating the formation of calcium chromate, had resulted in a distinct reduction in bronchial carcinoma mortality among workers exposed for the first time after the change-over (completed in 1958 in Leverkusen and 1964 in Uerdingen). A total of 1417 workers with at least 1 year of exposure were enrolled in the study. The observation period ended on 31 December 1988. The expected number of deaths was calculated using population statistics for North Rhine-Westphalia. The risk was determined in the form of a standardised mortality ratio (SMR), i.e. the ratio of observed deaths to expected deaths. In the group of 739 workers exposed before the process change-over was completed, 432 died during the observation period, 66 of them from bronchial carcinoma. This significant excess produced an SMR of 2.27 (95% confidence interval: 1.78-2.85). Where the cause of death was unknown, cases were allocated to a cause of death on the basis of the percentage occurrence of various causes of death in the specific subcohort. The cohort of 678 workers first exposed after the process modification had been completed had a slightly increased SMR for lung cancer of 1.26 (95% confidence interval: 0.58-2.38) based on nine cases.(ABSTRACT TRUNCATED AT 250 WORDS)

A multicentre mortality study of workers exposed to ethylene oxide.

A multicentre cohort study was carried out to study the possible association between exposure to ethylene oxide and cancer mortality. The cohort consisted of 2658 men from eight chemical plants of six chemical companies in the Federal Republic of Germany who had been exposed to ethylene oxide for at least one year between 1928 and 1981. The number of subjects in the separate plants varied from 98 to 604. By the closing date of the study (31 December 1982) 268 had died, 68 from malignant neoplasms. For 63 employees who had left the plant (2.4%) the vital status remained unknown. The standardised mortality ratio for all causes of death was 0.87 and for all malignancies 0.97 compared with national rates. When local state rates were used the SMRs were slightly lower. Two deaths from leukaemia were observed compared with 2.35 expected (SMR = 0.85). SMRs for carcinoma of the oesophagus (2.0) and carcinoma of the stomach (1.38) were raised but not significantly. In one plant an internal "control group" was selected matched for age, sex, and date of entry into the factory and compared with the exposed group. In both groups a "healthy worker effect" was observed. The total mortality and mortality from malignant neoplasms was higher in the exposed than in the control group; the differences were not statistically significant. There were no deaths from leukaemia in the exposed group and one in the control group.

Erythrocyte protein conjugates as a principle of biological monitoring for pesticides.

The determination of erythrocyte protein conjugates is recommended for monitoring worker's exposure to reactive pesticides or group of pesticides. Under the assumption that reversible and especially irreversible toxic effects of these substances occur in parallel to the formation of erythrocyte adducts, the determination of the amount of adduct can be seen as a parameter for monitoring stress and strain by these substances. The application of this method is demonstrated in some practical examples with several groups of compounds. In the case of unknown dose-effect relationships, the absence of conjugate formation in the erythrocyte initially will be considered as a no-toxic effect level, which can be substituted later by a tolerable substance-adduct concentration in the erythrocyte as more field experience has been gained. In contrast to the determination of chemicals and/or metabolites in the different body fluids, the examination of internal stress of substances by the determination of erythrocyte adducts has facilitated individual risk assessment for exposure to these substances. The appropriateness of individual tolerance values for active substances will be discussed. Sufficient valid and non-invasive methods are available for the routine detection of substance conjugates in erythrocytes.

Chromium bond detection in isolated erythrocytes: a new principle of biological monitoring of exposure to hexavalent chromium.

Internal stress to chromium is only relevant in occupational medicine if it is due to the handling of hexavalent chromium. Cr(VI) ions, after uptake by inhalation or percutaneously are carried in the blood plasma and penetrate--depending on the concentration--into the erythrocytes. Due to the intracellular reduction to Cr(III) and the concurrent intracellular protein binding, the erythrocytes represent an easily accessible target organ for quantitative chromium determination after occupational exposure to Cr(VI) compounds. The results of an earlier experimental study indicate that human plasma too is capable of spontaneous reduction of Cr(VI) ions of up to 2 ppm to Cr(III). This plasma reduction capacity (PRC) can be increased and accelerated considerably by adding ascorbic acid (AA). These findings were supported in this investigation by proving a decreased binding of Cr(VI) inside the erythrocytes under the effect of AA. This leads to the assumption that only those Cr(VI) concentrations can penetrate the membrane of the erythrocytes and enter the cell which either come into contact with the membrane during the reduction process or exceed this limit concentration of 2 ppm. Only in these two instances can corresponding chromium findings be analyzed in isolated and washed erythrocytes. These results are compared with those obtained by conventional methods, such as Cr determination in the blood and/or urine. Our findings indicate that a single determination of chromium concentration in the erythrocytes will permit the monitoring of critical cases of Cr(VI) exposure. This is a new type of biological monitoring in the sense of a condensed longitudinal study, in order to find out whether threshold concentrations have been respected over a given period.

Blood protein conjugates and acetylation of aromatic amines. New findings on biological monitoring.

Internal stress of aromatic amines has so far been evaluated by their determination in blood or urine and by the degree of methemoglobin formation. Animal experiments have shown that these materials can form adducts and conjugates with proteins and nucleic acids. Our investigations show that these processes can also occur in human metabolism. For this the degree of such a formation of protein conjugates depends on an individually different potential for acetylation. In a positive sense it influences the magnitude and the rate of renal excretion of aminoaromates and their conjugates and metabolites formed by this metabolism. In contrast, only free nonacetylated aminoaromates can lead to the formation of conjugates with hemoglobin. These aminoaromates or their metabolites can then be detected quantitatively in intact erythrocytes during their lifespan. The degree of this protein conjugate formation correlates inversely with the magnitude of the acetylation potential depending on the availability of free non-acetylated aminoaromates. According to these results a clearer assessment of past stress or the presence of strain can be obtained with Biological Monitoring by a single determination of such hemoglobin adducts rather than by the traditional quantitative determination of aminoaromates or their metabolites in blood and/or urine or the methemoglobin concentration.

Experimental bases for ascorbic acid therapy of poisoning by hexavalent chromium compounds.

The most frequent outcome of the usually transdermal absorption of hexavalent chromium compounds is uraemia due to tubular necrosis. We have confirmed earlier observations that this can be prevented by the immediate application of ascorbic acid (AA) with the aim of reducing Cr(VI) to Cr(III). The spontaneous reducing capacity of samples of serum and plasma for Cr(VI) compounds was polarographically determined to be about 2 ppm. Addition of AA in doses of 50 to 1000 ppm led to a rapid and dose-dependent reduction of chromium(VI), which was studied on the concentration level of 5 ppm. For example in the presence of 1000 ppm AA, five ppm chromium(VI) fade to 0.7 ppm within 20 min and to undetectable concentrations after 40 min. These experiments demonstrate the effectiveness of AA for the treatment of Cr(VI) poisoning. Reduction is increased and accelerated by AA and the resulting Cr(III)-protein complexes are non-toxic and can be excreted with the urine. Early and repeated high i.v. doses of AA are recommended as the therapy of choice for Cr(VI) poisoning. In cases of delayed medical treatment, AA should be immediately applied orally.

[The effect of an on the job training program -- stairclimbing -- on the physical working capacity of employees (author's transl)]. / Uber den Einfluss einer berufsnahen Trainingsmöglichkeit auf die körperliche Leistungsfähigkeit von Angestellten.

Following medical screening and physical fitness testing (W170) 52 voltuntary employees in a 31-story administration building were formed into matched pairs and randomly allocated into intervention (stairclimbing) and control (lift) groups. The intervention group was asked to climb at least 25 floors/workday or 125 floors/week. the control group was asked to use only the lift. The intervention time was 10 weeks. The physiological measurements were made before and after the intervention. The number of stairs climbed was recorded daily in a diary. The heart rate was recorded continuously over one workday before and during the interventions. The average quantity of training in the final intervention group (n = 19) was 29.9 floors/workday or 36,790 kpm/week and in the control group 4.6 and 5980 correspondingly. The average training frequency was 4.3 in intervention and 1.4 climbs/workday in the control group. The average number of continuous floors used during climbing was 7.0 in intervention and 3.4 in control group. The average number of minutes on heart rate level of 130-159 beats/min during one workday was 7.8 in intervention and 1.6 in control group. The W170 (W/kg) increased 17.8% and the predicted VO2max (ml/min/kg) 15.1% in intervention group. The difference between the intervention group and the control group was significant (p less than 0.01). It was concluded, that stairclimbing is a suitable on the job physical activity program for middle-aged, untrained men.