Primary particles and their agglomerate formation as modifying risk factors of nonfibrous nanosized dust.

The incidence of certain cancers correlates with the number of dust particles in the air. Nanosized particles differ from coarser particles by their increasing tendency to form agglomerates. The dissociation of biodurable agglomerates after deposition in the alveolar region resulted in a higher toxic potential. Biodurable dusts in the urban and workplace environment were analyzed to determine an effect-relevant exposure parameter. The characterization of the dusts relating to their number of primary particles (P(p)) and agglomerates and aggregates (A + A) was performed by electron microscopy. Diesel soot, toner material, and seven further dust samples in the workplace environment are composed of high numbers of nanosized primary particles (<100 nm) per unit mass occurring as larger agglomerates. Primary particles of rock, kaoline, and seven further dusts sampled in the workplace are not nanosized. In a multivariate analysis that predicted lung tumor risk, the mass, volume, and numbers of A + A and P(p) per milligram dust were shown to be relevant parameters. Dose-response relationships revealed an increased tumor risk in rats with higher numbers of P(p) in nanosized dust, which occurs unintentionally in the environment.

Classification of man-made vitreous fibers: Comments on the revaluation by an IARC working group.

In 2001, an IARC working group revaluated the carcinogenic risks of man-made vitreous fibers (MMVF). Compared with the IARC evaluation in 1987, the overall evaluations of insulation glass wool, rock (stone) wool, and slag wool were changed from Group 2B to Group 3. These changes ensued from an alteration in the evidence for cancer in humans and in experimental animals: Instead of "sufficient," the evidence for cancer in experimental animals is now looked upon as "limited" if there is a carcinogenic response after intraperitoneal injection but not after recently conducted inhalation experiments. For these studies, it is argued that they did properly address the technological limitations of earlier inhalation experiments. For Maxim and McConnell [Maxim L.D., McConnell E.E., 2001. Interspecies comparisons of the toxicity of asbestos and synthetic vitreous fibers: a weight-of-the-evidence approach. Regul. Toxicol. Pharmacol. 33, 319-342], well-conducted inhalation studies are very sensitive and rats may be more sensitive than humans in detecting the carcinogenic potential of MMVF. However, their arguments are highly questionable. The explanations of the IARC working group for preferring the newer inhalation studies are not sufficiently supported by the published data. Having in mind the higher sensitivity of humans compared to rats after inhalation of asbestos, more emphasis should have been given to the carcinogenic response after intraperitoneal injection.

Inorganic fibres in the lung tissue of Hungarian and German lung cancer patients.

OBJECTIVE: To ascertain the lung burden of asbestos fibres in Hungarian lung cancer patients in comparison with the cumulative asbestos exposure estimated from the occupational history. METHODS: For 25 Hungarian lung cancer patients, lung tissue fibre analysis was performed by scanning transmission electron microscopy (STEM) and counting of ferruginous bodies (FBs) by light microscopy. Cumulative asbestos exposure in fibre-years was assessed from a standardised occupational history using the report "fibre years" of the German Berufsgenossenschaften. RESULTS: Median and maximum concentrations of fibres longer 5 microns per gram dry lung tissue (g dry) were 0.03 and 7.38 million fibres/g dry for chrysotile, 0.00 and 0.21 million fibres/g dry for amphibole and 0.22 and 0.62 million fibres/g dry for other mineral fibres (OMFs). The maximum values were observed in one patient for whom a high asbestos exposure was evident in advance from the occupational history. CONCLUSIONS: In comparison with reference values obtained by the same method for German patients with no indication of workplace asbestos exposure, increased concentrations of more than 0.2 million chrysotile fibres/g dry were obtained for six of the 25 Hungarian patients (24%). For one of them, the second highest estimate of a workplace exposure of 60 fibre-years and the highest tissue concentration of 7.38 million chrysotile fibres/g dry substantiate a high probability of a causal relationship to asbestos. A further comparison can be made with the results for 66 German patients treated by surgical lung resection for a disorder other than mesothelioma, mainly lung cancer. For the Hungarian lung cancer patients, similar amounts of chrysotile but distinctly lower amounts of amphibole fibres and distinctly higher amounts of OMFs were observed. A correlation between exposure estimates from occupational history and concentration of fibres in the lung tissue was observed for amphibole (Spearman: R = 0.66, P < 0.001, Pearson: R = 0.50, P = 0.01) and for chrysotile (Pearson: R = 0.48, P = 0.02).

Asbestos and man-made vitreous fibers as risk factors for diffuse malignant mesothelioma: results from a German hospital-based case-control study.

BACKGROUND: This study examines the role of occupational factors in the development of diffuse malignant mesothelioma with special emphasis on the dose-response relationship for asbestos and on the exposure to man-made vitreous fibers (MMVFs). METHODS: One hundred and twenty-five male cases, diagnosed by a panel of pathologists, were personally interviewed concerning their occupational and smoking history. The same number of population controls (matched for sex, age and region of residence) underwent similar interviews by trained interviewers. Odds ratios (OR) were calculated for an expert-based exposure index using conditional logistic regression. RESULTS: Exposure to asbestos shows the expected sharp gradient with an OR of about 45 for a cumulative exposure > 1.5 fiber years (arithmetic mean 16 fiber years). A significant OR was calculated even for the lowest exposure category "> 0 - < or = 0.15 fiber years". Although the mean cumulative exposure to MMVF is roughly 10% of the exposure to asbestos, an increased OR is observed in an ever/never evaluation. This observation is heavily hampered by methodical problems. A corresponding case-control study was performed using a lung tissue fiber analysis in addition to interviews. Both interviews and the lung tissue analysis yielded similar OR levels between the reference and the maximum exposure intervals. CONCLUSIONS: Despite a possible influence as a result of selection and information bias, our results confirm the previously reported observation of a distinct dose-response relationship even at levels of cumulative exposure below 1 fiber year. Moreover, the study confirms that asbestos is a relevant confounder for MMVF. A causal relationship between exposure to MMVF and mesothelioma could neither be detected nor excluded, as in other studies.

Pleural mesothelioma associated with indoor pollution of asbestos.

This case report concerns a 46-year-old woman, dying from histologically confirmed diffuse malignant mesothelioma after asbestos exposure, which was only caused by indoor pollution from crocidolite-containing spray asbestos in building materials. There was no other known occupational or environmental asbestos exposure during her life. The lung tissue fibre analysis by light microscopy showed significantly increased concentrations of ferruginous bodies (3162 FB per gram of wet lung tissue). By use of scanning transmission electron microscopy, clearly increased concentrations of amphibole fibres (8.6 x 10(6) fibres longer than 1 microm and 0.6 x 10(6) fibres longer than > or =5 microm per gram dry tissue), mainly classified as crocidolite, were observed. The disease was attributed to indoor exposure to sprayed asbestos, which occurred during her work as a decorator in the studio of a warehouse.

Role of occupational asbestos exposure in Hungarian lung cancer patients.

OBJECTIVE: What is the frequency of occupational asbestos exposure among patients suffering from malignant respiratory tumours and how many of these tumours are associated with asbestos in Hungary? METHODS: An internationally established questionnaire with 29 questions, covering the most characteristic activities of asbestos exposure at the workplace was completed for 300 patients with respiratory malignancies, i.e. 297 patients with lung cancer and three with mesothelioma of the pleura. From the questionnaire, the smoking habits were estimated and cumulative asbestos exposure was assessed in fibre-years. Additionally, lung X-rays were classified and the national data on the incidence of malignant pleura mesothelioma were analysed. RESULTS: A cumulative asbestos exposure of 25 fibre-years or more was detected in 11 patients with lung cancer (4%) and in each of the three patients with pleural mesothelioma (100%). In a further 72 patients (24%), cumulative occupational asbestos exposure was assessed as below 25 fibre-years (between 0.01 and 23.9 fibre-years). In this group, car and truck mechanics, and installation and construction workers using asbestos-cement were registered. Among patients with an asbestos exposure of 25 fibre-years or more, six asbestos-cement production workers were observed, among them the three mesothelioma cases. A weak but significant association between positive X-ray findings and exposure estimates could be demonstrated. Additionally, results of the lung tissue fibre counts by scanning transmission electron microscopy were available for 25 of the lung cancer patients. A good correlation was observed between the asbestos fibre counts and the assessment of cumulative asbestos exposure. In Hungary, 84 cases of pleural mesothelioma were registered in 1997 and 73 in 1998. These numbers correspond to an annual incidence of about one new case per 100,000 inhabitants older than 15 years. CONCLUSIONS: The annual incidence of lung cancer in Hungary is about 6,000. Since in our series of lung cancer patients about 4% were observed, which could be accepted as representing occupational disease because of a cumulative exposure to 25 fibre-years or more, the annual asbestos related lung tumour incidences may be estimated to be approximately 150 or more. The proportion of nearly two estimated cases of lung cancer per case of pleural mesothelioma corresponds to international experience. Up to now, lung cancer cases only exceptionally have been registered as occupational diseases, i.e. they were seriously under-diagnosed in Hungary. For improving this situation, diagnostic assistance by a self-interview with a questionnaire covering the working history for all newly diagnosed lung cancer patients would be helpful.

Dose-response relationship between amphibole fiber lung burden and mesothelioma.

In a mesothelioma case-control study, asbestos and other mineral fibers from lung burden were examined as causal factors. Diagnosis was confirmed by a panel of pathologists. For 66 cases and 66 controls from hospitals in five German towns, lung tissue fiber analysis by transmission electron microscopy was available. Control patients were treated by a surgical lung resection mostly because of lung cancer. For chrysotile and other mineral fibers a significantly increased odds ratio (OR) was not observed. A clear dose-response relationship was demonstrated for the concentration CA of amphibole fibers longer than 5 microm. Between 0.025 and 2.5 fibers/microg dry weight (f/microg) the relationship can be approximated as OR = CA/(0. 025 f/microg). Similar but less distinct dose-response relationships were found in a Canadian and an Australian study. It is concluded that among German mesothelioma patients factors not associated with amphibole fiber concentration are not predominating.

Environmental exposure to tremolite asbestos: pleural mesothelioma in two Turkish workers in Germany.

This report concerns two Turkish immigrant workers, aged 50 and 59, who developed histologically confirmed diffuse malignant mesothelioma in the absence of obvious occupational exposure to asbestos in Germany. Both patients had spent their childhood in central Anatolia, Turkey, where the presence of tremolite asbestos in the environment has been described. In both patients, the lung-dust burden showed a high concentration of amphibole fibers (186 x 10(6) resp. 59 x 10(6) per gram dry tissue), mainly classified as actionolite/tremolite fibers in scanning transmission electron microscopy. In both patients, the disease was thus attributed to early environmental exposure to tremolite asbestos.

[Environmental and indoor air exposure to asbestos fiber dust as a risk and causal factor of diffuse malignant pleural mesothelioma]. / Umwelt- und Innenraum-Gefährdung durch Asbestfaserstaub als Risiko- und Einflussfaktor des diffusen malignen Pleuramesothelioms (DMM).

In an interdisciplinary, multicentre case control study of the causal factors of the diffuse malignant mesothelioma (DMM) standardised histories where taken from n = 324 Patients suffering from DMM, n = 315 hospital control patients (KK) and n = 182 population controls (PK). For 66 DMM, 149 KK and 107 PK a risk from asbestos fibre dust at the workplace was not detectable. For latter persons indoor and outdoor asbestos exposure outside of the workplace were investigated. The following factors were examined: neighbourhood exposure from companies using asbestos, living in big cities and nearby main traffic roads, building materials containing asbestos, electric storage heaters and household contacts. For using electric storage heaters a statistically significant increased odds ratio (OR) was observed for DMM as well in comparison with KK (OR = 2.42; 95%-CI: 1.01-5.72) and in comparison for PK (OR = 2.91; 95%-CI: 1.08-7.80). Only outside of Hamburg an increased OR compared to KK was observed for people living in the neighbourhood of asbestos factories (OR = 16.3; 95%-CI: 1.35-196.8) and also, but only in Hamburg, compared to PK living nearby main traffic roads. There is only a trend for a mesothelioma-risk for household-contacts based on a few cases. In one DMM-patient without an occupational asbestos exposure the lung dust fibre analysis yielded 2.912 FB and 1.459 x 10(3) crocydolithe fibres per gram dried lung tissue. As a child he lived in the immediate vicinity of the blue asbestos mine in Wittenoom, Australia. Therefore in special cases a para-occupational asbestos or a neighbourhood asbestos exposure can be demonstrated as a risk factor of diffuse malignant mesothelioma.

Airborne fibre concentrations and lung burden compared to the tumour response in rats and humans exposed to asbestos.

The excess risk of tumours exposed to asbestos were previously compared with the results of rat inhalation experiments. It could be demonstrated that humans at the workplace suffer from a tumour risk at fibre concentrations which are 300 times lower than those needed in the rat inhalation model to produce the same risk. However, the estimation of human risk was based on the study of workers at a chrysotile textile factory, whereas animal experimental results were related to exposure to amphiboles. Since for this comparison the risk of cancer due to exposure to amosite or crocidolite fibres at the workplace is of interest, quantitative exposure-response relationships for lung cancer and mesothelioma for the white workforce of South African amosite and crocidolite mines were discussed. On comparing the risk of lung cancer in this study with the risk of lung cancer for chrysotile textile workers, it can be concluded, that the risk of lung cancer and mesothelioma from crocidolite and amosite was higher than in the chrysotile textile factory. It could be also demonstrated, on the basis of a study of the lung burden of mesothelioma cases and of controls, that a significantly increased odds ratio of about 5 was established at amphibole concentrations of between 0.1 and 0.2 f micrograms-1 dry lung (WHO fibres longer than 5 microns from TEM analysis). On the other hand, carcinogenic response was observed at a fibre concentration 6000 times higher in animal inhalation experiments with crocidolite asbestos (SEM analysis of WHO fibres). As a result of these findings, it has been concluded that inhalation studies in rats are not sufficiently sensitive for the detection of hazards and risks to humans exposed to man-made fibres.

Mortality rates in a female cohort following asbestos exposure in Germany.

A cohort study was conducted of 616 German female workers with a history of exposure to asbestos. Standardized proportionate mortality analysis was done except for mesothelioma, for which proportionate mortality was computed based on best evident cause of death. Mortality from lung cancer was increased three times over expected value. Death rates due to mesothelioma were 340 times higher than in the general population. Female mortality rates surpassed those observed in men twofold for lung cancer and fourfold for mesothelioma. In comparison with published data from international cohort studies, the observed mortality for mesothelioma in our female cohort appeared higher than that previously reported. German women with a history of asbestos exposure are considered a high-risk group for developing mesothelioma and lung cancer. They should be a target group for intervention strategies (eg, chemoprevention, smoking cessation, early cancer detection).

Measurement of inorganic fibrous particulates in ambient air and indoors with the scanning electron microscope.

In the Federal Republic of Germany, the concentration of inorganic fibrous particles in the ambient air is measured by scanning electron microscopy (SEM) in accordance with draft guideline VDI 3492. Fibres of length greater than or equal to 2.5 microns are counted at a magnification of X2000. The concentrations and fibre dimensions of asbestos fibres and other mineral fibres were determined for 231 ambient air samples, 219 indoor air samples taken during asbestos removal and 21 taken at workplaces. In the ambient air measurements in rural and urban areas, the average concentration of other inorganic fibres was greater than 1000 fibres of length greater than or equal to 5 microns per m3. On the average, only about 100 or fewer asbestos fibres of length greater than or equal to 5 microns per m3 were observed. These 'asbestos fibres' from ambient air had low aspect ratios. They differed substantially from asbestos fibres measured in the ambient air close to sources of asbestos emissions, indoors during asbestos removal or at workplaces. Furthermore, the size distribution of these 'asbestos fibres' was similar to that of 'other inorganic fibres'. We suggest, therefore, that a substantial portion of the 'asbestos fibres' observed by SEM analysis in ambient air samples from rural and urban areas should be classified instead as 'other mineral fibres'.

Evaluation and application of a plasma ashing method for STEM fiber analysis in human lung tissue.

A preparation technique for fiber analysis in human lung tissue has been developed that involves freeze-drying and low-temperature ashing. Analysis is made in the analytical scanning transmission electron microscope at a magnification of 10,000 x. With the use of a special counting method, the sensitivity is approximately 80,000 fibers per gram dry tissue with lengths less than 5 microns and 40,000 fibers per gram dry tissue with lengths greater than or equal to 5 microns. In spite of the leaching and contamination effects described in the literature--even for chrysotile fibrils taken from the lung, elemental spectra do not differ essentially from the asbestos standard. In order to carry out a complete check of the preparation method, a suspension of standard crocidolite fibers in water was gelatinated. No changes in length, diameter or aspect ratio distribution occurred. After preparation, at least 40% of the fibers were recovered. Compared to the wide range of fiber concentrations observed in human lung tissue, these recovery rates appear adequate for fiber analysis in lung dust for medical or legal purposes. To date, 70 lung dust specimens have been analyzed. These are discussed in the paper.

Potential health risks from the use of fibrous mineral absorption granulates.

Attapulgite (palygorskite) and sepiolite are fibrous clay minerals used commercially as components in a wide variety of products including oil and grease adsorbents, carriers for pharmaceuticals, cosmetics, and pesticides. They are also components of drilling muds and animal litter and they are used as paint thickeners. The current annual worldwide production of these minerals exceeds one million tons. Although fibrous in nature, the fibre length may vary greatly depending on the location of the geological deposits. American attapulgite is short (0.1-2.5 micron in length, median of 0.4 micron) but palygorskite from other parts of the world is much longer (30% longer than 5 micron). Several samples of these materials have been submitted to scanning transmission electron microscopy (STEM). This paper reports the results of microscopic evaluations and makes a comparison with the data from experimental carcinogenicity studies and it is concluded that fibre length is a most important carcinogenic property.