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.

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.

The article contains sections titled: 1. Introduction 2. Chromium Ores 2.1. Ore Deposits 2.2. Ore Beneficiation 3. Production of Sodium Dichromate 3.1. Alkaline Roasting 3.2. Leaching of the Roast 3.3. Acidification 3.4. Crystallization 4. Chromium Oxides 4.1. Chromium(III) Oxide and Chromium Hydroxide 4.2. Chromium(IV) Oxide (Chromium Dioxide) 4.3. Chromium(VI) Oxide 5. Chromium(III) Salts 5.1. General Properties 5.2. Chromium(III) Sulfates and Chrome Tanning Agents 5.3. Other Chromium(III) Salts 6. Chromic Acids and Chromates(VI) 6.1. Chromic Acids 6.2. Alkali Chromates and Dichromates 6.3. Other Chromates 7. Other Chromium Compounds 8. Analysis 9. Transportation, Storage, and Handling 10. Environmental Protection 11. Ecotoxicology 12. Nutrition 13. Toxicology and Occupational Health 14. Economic Aspects

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.

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. The possibility of raised rates of miscarriages for women engaged in EO sterilisation in hospital has also been discussed.5Two Swedish studies have reported a raised SMR for leukaemia.67 In one of these studies an additional raised rate from stomach carcinoma was also mentioned. A further study reported one case each of myelogenous leukameia and lymphosarcoma.'In a fourth study, however, no case of leukaemia was observed.9 The question ofthe carcinogenicity of EO for man therefore still remains open; this view is confirmed by more recent reviews.'0 1These differing published observations induced the Verband der Chemischen Industrie (VCI) to start its own study of exposure to EO in its member companies. The aim was the investigation of a possible association between exposure to EO and mortality (total mortality and mortality due to leukaemia or other types of neoplasms). The investigation was carried out by means ofhistoric cohort study with the calculation of SMRs. Methods and materials STUDY DESIGNSince only relatively few employees exposed to EO could be included in an epidemiological study from each producer or processor of EO in the Federal Republic of Germany it was decided to conduct a multicentre study in eight plants of the chemical industry.* All members of the cohort formed had to The inquiry into the causes of death had to be carried out within the narrow limits given by the German data protection legislation and also was subject to the relevant laws of the penal code and those paragraphs of the medical code concerning professional secrecy.By following this procedure completeness of the information was obtained to a large extent. For the statistical evaluation the data sheets have been made anonymous. CODING OF CAUSES OF DEATH