A 51 yr old, nonsmoking female suffered from relapsing progressive pneumonia for several years. The patient had worked for 16 yrs in the nuclear industry and was exposed to grinding particles and welding fumes working with zirkaloy, an alloy containing tin, iron, chromium and zirconium. During an exacerbation of the pneumonia radiography of the lung showed interstitial infiltrations of both lower lobes. Extended diagnostic procedures could not confirm an infectious disease. In addition, nodular and painful thickenings appeared in old operation scars on the left breast and right hand, and near former injection points on the buttocks and abdominal wall. The scar tissue of the left breast and an axiliary lymph node were examined histologically after excision. Both tissues showed many epithelioid cell granulomas with giant cells, while foreign bodies were only seen in the skin. Persistent infiltrations of the lung led to lobectomy of the right lower lobe and partial resection of the middle lobe in order to exclude a malignant disease. The histological picture of the lung tissue showed different stages of alterations with pronounced proliferation of the alveolar epithelium, epithelioid cell granulomas between well-presented alveolar walls and additional large areas of scarred tissue [1]. Regression of the pulmonary infiltrations was observed within a few weeks of beginning corticosteroid therapy with 24 mg prednisone daily. The initial pulmonary function test showed a normal vital capacity and a reduced timed vital capacity (Tiffeneau test), which was normal in a control examination 6 months later.Zirconium is a noncorrosive material which is used as pure metal or alloy in, for example, the aircraft, aerospace and nuclear industries [2]. It is known from both human experience [3] and animal studies [4] that zirconium can cause hypersensitivity reactions of the skin with epithelioid cell granulomas after repeated topical application of deodorants containing soluble and insoluble zirconium salts. Pulmonary alterations such as radiographic shadows, granulomas and interstitial fibrosis were observed in animal studies after zirconium exposure [5][6][7]. In humans pulmonary alterations are reported only rarely [8][9][10][11][12]. There are only a few case reports of zirconium-related lung diseases, in particular pulmonary granulomatous alterations [11,12].In order to confirm zirconium as the causative agent of the disease, lung tissue was examined by scanning transmission electron microscopy. Intracellular particles in lung granulomas could be identified as zirconium, along with iron, chromium and silicon [13]. Beryllium, a possible occupational agent which is able to induce granulomas, could not be found.Nearly 10 yrs after the diagnosis [1, 13] the patient was free of complaints under ongoing therapy with 6 mg prednisone daily and suffered from a mild obstructive lung disease. The granulomatous disease was regarded as valid for compensation by the German occupational accident insurances.Most cohort studies in workers exp...

The oncogene product epidermal growth factor receptor (EGF-R), the tumour suppressor gene product p53 and anti-p53 antibodies are detectable in the serum of certain cancer patients. Increased levels of some of these products were reported in lung cancer patients after occupational asbestos exposure and after exposure to polycyclic aromatic hydrocarbons or vinylchloride. In the first step, this study investigated the possible diagnostic value of serum EGF-R, p53-protein and anti-p53 antibodies, measured by an enzyme-linked immunosorbent assay, in lung tumour patients. In addition to being investigated on a molecular epidemiological basis, these parameters were examined as biomarkers of carcinogenesis, especially with regard to asbestos incorporation effects or of radon-induced lung cancers. Also, a possible effect of cigarette smoking and age dependence were studied. A total of 116 male patients with lung or pleural tumours were examined. The histological classification was four small-cell cancers, six large-cell cancers, 32 adenocarcinomas, 47 squamous carcinomas, 12 mixed lung carcinomas, five diffuse malignant mesotheliomas and ten lung metastasis of extrapulmonary tumours. Twenty-two lung cancers and all mesotheliomas were related to asbestos, 22 lung cancers were related to ionizing radiation and 61 patients had cigarette smoke-related lung cancer. Besides these patients 50 male patients with non-malignant lung or pleural diseases were included; of the latter eight subjects suffered from asbestosis. Controls were 129 male subjects without any lung disease. No significantly elevated or decreased serum values for p53 protein, EGF-R, or anti-p53 antibodies as a function of histological tumour type, age, or degree and type of exposure (asbestos, smoking, ionizing radiation) could be found. The utility of p53-protein, EGF-R and anti-p53 antibodies as routine biomarkers for screening occupationally derived lung cancers is limited. © 1999 Cancer Research Campaign

In 1972, a procedure was introduced by the Industrial Injuries Insurance Institutes (Berufsgenossenschaften) of the Federal Republic of Germany, which is to be used by the special occupational health service for employees exposed to asbestos dust. Since 1 January 1972, occupational health examinations are performed when exposure to asbestos dust has been of at least 3 years' duration. On 1 January 1977, a prospective cohort study was started with employees formerly exposed to asbestos dust whilst working for companies manufacturing or using asbestos. Data on these persons are collected in the Central Register of Employees Exposed to Asbestos Dust of the Industrial Injuries Insurance Institutes. A total of 3,070 male and female employees in whom asbestos exposure terminated after 1 January 1972 formed subcohort I of the study. For comparison, 665 persons whose exposure terminated before 1 January 1972 served as subcohort II. In addition to several other inclusion criteria, each individual's permission was required before personal data could be evaluated. Of the subjects in the two subcohorts, 185 and 71, respectively, had died by 31 December 1982. Tumours were more frequently than this cause of death is expected in the general population. In addition to a high incidence of mesothelioma, the standard mortality rate was especially increased for lung cancer. The proportional mortality rates of about 40% for tumours of all sites (with about 17% lung cancer and 8% mesothelioma) especially in subcohort II, seemed to be comparable to the international figures for epidemiological mortality.

Man-made mineral fibers (MMMF) (ceramic fibers), which were used as insulation material in industrial furnaces at temperatures ranging between 1, OOO and 1, 240"C, were investigated. New phases with demonstrated biologic activity were detected. Formation of cristobalite and mullite phases could be identified by polarised light microscopy, (with the help of color immersion methods for phase contrast), as well as X-ray diffraction and electron microscopy.Experimental investigations on MMMF (vitreous and ceramic fibers) demonstrate that recrystallization begins to occur at temperatures as low as 150°C at relatively low water vapor pressures, e.g., 5 bars (Fig. 1).Quantitative electron microscopic investigation of the suspension of a sample treated with water vapor at a temperature of 150°C over a period of 20 days showed the following results (enlargement: 10,OOO-fold): ca 40 * lo6 F/mg of all lengths, and 6 -lo6 F/mg of lengths > 5 pm.The elemental composition of silicon (Si) and aluminum (A), as well as the unstable diffraction pattern in the electron beam, all point to the formation of fibers of zeolite composition. The fiber-size distribution of the new crystalline product shows them to possess dimensions of L 2 5 pm and D 2 0.5 pm (Fig. 1). These sizes are important to consider in cytotoxicity, fibrogenicity, and oncogenic effects.At temperatures of 2 200°C, chrysotile fibers appear to form. After a reaction time of 10 days at 30O"C, chrysotile fibers with the following size distributions were observed: 1.5 * lo6 F/mg of all lengths, and 0.5 * lo6 F/mg of lengths > 5 pm.

Due to latency periods that can last for decades, asbestos-related diseases show 18 years after the enforcement of the prohibition of asbestos application in Germany their highest numbers. In the centre of attention are asbestos-induced pleural fibroses, mesotheliomas, asbestoses, lung and laryngeal cancer. Diagnosing and expertizing these diseases causes difficulties, is hitherto non-uniform and does frequently not correspond to the current medico-scientific expertise. This induced the German Respiratory Society as well as the German Society of Occupational and Environmental Medicine in cooperation with the German Society of Pathology, the German Radiology Society and the German Society of Otorhinolaryngology, Head and Cervical Surgery, to develop the above mentioned guideline during seven meetings moderated by AWMF. The required thorough diagnosis is based on the detailed recording of a qualified occupational history. Since the sole radiological and pathological-anatomical findings cannot sufficiently contribute to the causal relationship the occupational history recorded by a general physician and a specialist is of decisive importance. These physicians have to report suspected occupational diseases and to advise patients on social and medical questions. Frequently, problems occur if the recognition of an occupational disease is neglected due to a supposedly too low exposure or too few ferruginous bodies or low fibre concentrations in lung tissue. The new S2k directive summarizing the current medico-scientific knowledge is for this reason, for diagnoses and expert opinions as well as for the determination of a reduced capacity for work a very important source of information.