Abstract  During the 1990s, research activities to characterise environmental health risks grew significantly in France, providing useful tools for policy-makers in this field. Research into the management of these risks also exists, but is neither coherent on a national scale nor sufficient to deal with the issues created by the accelerated production of potentially anxiety-inducing scientific information. This article focuses on the study of public policies in environmental health and is intended to contribute to development of knowledge in this domain. Reviewing explanatory approaches to the construction of public risk management policies reveals three broad categories: “type of risk” or technical approaches that focus on ways to transform scientific knowledge into decision tools\; “public preferences and attitudes” approaches, which suggest that risk management policies are determined (or should be) by public demands\; and “interest group” approaches arguing that risk regimes are the product of the influences of various organised interests. Christopher Hood has developed a method to assess the relative weight of these approaches in actual risk regulation regimes, depending on situations and types of risks, and to analyse these regimes and compare those expected for each approach. We apply this method to French risk management policies for three risks — waterborne lead, exposure to Legionella in hotels, and exposure to asbestos in buildings. Conclusions of this explanatory exercise are consistent with Hood’s findings and point out the major relevance of the “interest groups” model, except in the area of asbestos, for which anticipation of public opinion seems to dominate. This exercise, although it may lack robustness, deserves further development to improve our understanding of the construction of environmental health policies.

Abstract  Malignant mesothelioma (MMe) is a seemingly uncommon tumour whose incidence has in fact increased steadily and progressively over the last 30 years. Indeed, an actual "epidemic" is expected in the next 20 years, with over 1300 new cases a year till 2020 at least. Despite unquestionable improvement in the diagnostic methods at our disposal and the availability of new treatment strategies, the prognosis of MMe patients remains dramatically poor. For all the above reasons, translational research is the key to success; indeed, ever increasing knowledge of the molecular mechanisms underlying MMe pathogenesis could lead (and is actually leading) to new, hopefully more active, treatment options. To foster discussion among investigators working in this field, and to exchange different viewpoints concerning the newest advances in MMe pathogenesis and treatment, the VII International Mesothelioma Interest Group (IMIG) meeting was held in Brescia (Italy) between 24 and 26 June 2004 in cooperation with the Italian Group for the Study and Therapy of MMe (GIMe). The aim of this report is to summarize the most significant advances in the different disciplines applied to MMe presented and discussed during the IMIG meeting and how these advances will be changing the perspective of patients with MMe.

Abstract  Nanomaterials are commonly defined as particles or fibers of less than 1 µm in diameter. For these reasons, they may be respirable in humans and have the potential, based upon their geometry, composition, size, and transport or durability in the body, to cause adverse effects on human health, especially if they are inhaled at high concentrations. Rodent inhalation models to predict the toxicity and pathogenicity of nanomaterials are prohibitive in terms of time and expense. For these reasons, a panel of in vitro assays is described below. These include cell culture assays for cytotoxicity (altered metabolism, decreased growth, lytic or apoptotic cell death), proliferation, genotoxicity, and altered gene expression. The choice of cell type for these assays may be dictated by the procedure or endpoint selected. Most of these assays have been standardized in our laboratory using pathogenic minerals (asbestos and silica) and non-pathogenic particles (fine titanium dioxide or glass beads) as negative controls. The results of these in vitro assays should predict whether testing of selected nanomaterials should be pursued in animal inhalation models that simulate physiologic exposure to inhaled nanomaterials. Conversely, intrathoracic or intrapleural injection of nanomaterials into rodents can be misleading because they bypass normal clearance mechanisms, and non-pathogenic fibers and particles can test positively in these assays.

Abstract  To investigate factors related to lung cancer mortality in six Arizona copper smelter towns, we identified 185 lung cancer cases and two matched controls per case from decedent residents during 1979-1990. Detailed information on lifetime residential, occupational, and smoking history was obtained by structured telephone interviews with knowledgeable informants. Interviews were completed for 82% of 183 eligible cases and 88% of the targeted number (366) of controls. Estimated historical environmental exposures to smelter emissions, based on atmospheric diffusion modeling of measured SO2 concentrations, were linked with residential histories to derive individual profiles of residential exposure. Occupational histories were characterized by potential exposure to smelter emissions, asbestos, and ionizing radiation. Conditional logistic regression was used to compare study factors in cases and controls with adjustment for potential confounding factors: gender, Hispanic ethnicity, and smoking. In overall and gender-specific analyses, no statistically significant associations were observed between lung cancer risk and any of the measures of residential exposure to smelter emissions considered (town of residence at time of death, highest level of exposure, and duration or cumulative exposure above background levels), or any of the estimated occupational exposures (definite or potential asbestos, potential ionizing radiation, definite or potential smelter). Among male residents of some, but not all, towns, there was some evidence of a positive association between lung cancer risk and reported copper smelter-related employment (reported as definite), with the highest risk observed for Miami, Arizona. This study provided little evidence of a positive association between lung cancer mortality and residential exposure to smelter emissions. Specific factors associated with the apparent heterogeneity in lung cancer risk across study towns cannot be identified in this community-based study.

Abstract  Nanomaterials of carbon origin tend to form various shapes of particles in micrometer dimensions. Among them, multi-wall carbon nanotubes (MWCNT) form fibrous or rod-shaped particles of length around 10 to 20 micrometers with an aspect ratio of more than three. Fibrous particles of this dimension including asbestos and some man-made fibers are reported to be carcinogenic, typically inducing mesothelioma. Here we report that MWCNT induces mesothelioma along with a positive control, crocidolite (blue asbestos), when administered intraperitoneally to p53 heterozygous mice that have been reported to be sensitive to asbestos. Our results point out the possibility that carbon-made fibrous or rod-shaped micrometer particles may share the carcinogenic mechanisms postulated for asbestos. To maintain sound activity of industrialization of nanomaterials, it would be prudent to implement strategies to keep good control of exposure to fibrous or rod-shaped carbon materials both in the workplace and in the future market until the biological/ carcinogenic properties, especially of their long-term biodurability, are fully assessed.

Abstract  This study reports on personal airborne lead exposure levels of workers removing windows painted with lead-based paint (LBP) and having asbestos caulking. Abatement/Removal of windows with LBP and asbestos caulking is becoming a common practice in the United States by environmental firms. As a result of both asbestos and lead regulations, many state regulatory agencies are categorizing this type of work as abatement and specification requirements are being issued for such work. However, little information has been published on exposure levels to asbestos and lead during various work practices. Exposure results presented in this study provide some historical (objective) data for abatement of windows with asbestos-containing materials (ACM) and LBP.

Abstract  Particulate pollutants have been suggested as a risk factor for increase in mortality and morbidity in patients with obstructive airway disease. In the present study we hypothesized that enhanced particle deposition dose is an underlying factor for such a finding. We measured lung deposition in normal healthy control subjects (N; n = 10) and in subjects with varying levels of airway obstruction: smokers (S; n = 10), smokers with small airways disease (SAD; n = 10), asthmatics (A; n = 5), and patients with chronic obstructive airway disease (COPD; n = 10). The subjects inhaled a uniform size sebacate aerosol (1-micron diameter) from a collapsible bag of a known volume (500 ml) repeatedly for as many as 15 breaths at a rate of 30 breaths/min. Aerosol concentration was monitored continuously at the mouth by a laser aerosol photometer. After correcting for particle loss in the bag, lung deposition fraction [DF = (inhaled minus exhaled)/inhaled], was determined breath by breath. DF values (mean +/- SD) were 0.14 +/- 0.02, 0.16 +/- 0.02, 0.21 +/- 0.05, 0.22 +/- 0.02 and 0.028 +/- 0.03 for N, S, SAD, A, and COPD, respectively. DF values in S, SAD, A, and COPD were 16, 49, 59, and 103% greater, respectively, than that of normal subjects (p < 0.05). DF of COPD was also greater than that of SAD or A (p < 0.05). No difference was found between SAD and A. When all of the subject data were combined, DF was correlated well with percent predicted FEV1 and FEF25-75 (r2 = 0.63 in both). The results indicate a marked increase in particle deposition in patients with obstructive lung disease, and this can be an important factor for the development of the adverse health effects of pollutant particles on the one hand and for the treatment of patients with drug aerosols on the other.

Abstract  Interstitial fibrosis resulting from workplace exposure to asbestos and crystalline silica persists throughout the world despite knowledge of the causes and effective means for prevention. Asbestosis and silicosis occurrence is predictable among people overexposed to dusts in various industries and occupations such as mining, construction, manufacturing, and building maintenance. Asbestosis and silicosis are incurable and may be progressive even after dust exposure has ceased, therefore early recognition and supportive interventions are important. Although current disease is a result of past exposures, effective control of current workplace exposures is the only way to prevent continued occurrence of these potentially debilitating diseases. Physicians can contribute to this effort through accurate diagnosis and disease reporting.

Abstract  Background and objective: This study describes the epidemiology of malignant pleural mesothelioma (MPM) in a rural population with environmental asbestos exposure. Methods: Patients with diagnosed MPM were recruited and their relevant demographic and exposure data were analysed. Results: A total of 131 patients with MPM (59 men, 72 women) were studied. The patients' mean age was 57.8 years and the mean exposure duration was 28.9 years. The cumulative fibre count of the villagers ranged from 0.19 to 14.61 fibre/mL-years. Of the 131 patients, 85 had epithelial cell type, 20 had mixed, and eight had sarcomatous pleural mesothelioma. No significant relationship was found between asbestos fibre type and age, exposure period, or cellular type of MPM; similarly, no significant relationship could be found between the cellular type and age or exposure period. Patients with sarcomatous mesotheliomas were considerably older. Only five of 131 (3.8%) patients had a family history of mesothelioma. Conclusions: Environmental exposure to asbestos begins at birth and this may be important in the age of disease onset, if a threshold model for cancer initiation is operative. Both men and women had an excess risk of mesothelioma. Given that a family history of MPM was not common in this relatively homogenous patient group, a genetic predisposition to mesothelioma appears unlikely.

Abstract  Prolonged exposure to high levels of silica has long been known to cause silicosis This paper evaluates the evidence for an increased risk of chronic obstructive pulmonary disease (COPD) in occupations and industries in which exposure to crystalline silica is the primary exposure, with a focus on the magnitude of risks and levels of exposure causing disabling health effects. The literature suggests consistently elevated risks of developing COPD associated with silica exposure in several occupations, including the construction industry; tunneling; cement industry; brick manufacturing; pottery and ceramic work; silica sand, granite and diatomaceous earth industries; gold mining; and iron and steel founding, with risk estimates being high in some, even after taking into account the effect of confounders like smoking. Average dust levels vary from about 0.5 mg.m3 to over 10 mg.m3 and average silica levels from 0.04 to over 5 mg.m3, often well above occupational standards. Factors influencing the variation from industry to industry in risks associated with exposure to silica-containing dusts include (a) the presence of other minerals in the dust, particularly when associated with clay minerals; (b) the size of the particles and percentage of quartz; (c) the physicochemical characteristics, such as whether the dust is freshly fractured. Longitudinal studies suggest that loss of lung function occurs with exposure to silica dust at concentrations of between 0.1 and 0.2 mg.m3, and that the effect of cumulative silica dust exposure on airflow obstruction is independent of silicosis. Nevertheless, a disabling loss of lung function in the absence of silicosis would not occur until between 30 and 40 years exposure.

Abstract  Malignant mesotheliomas (MMs) are aggressive tumors that develop most frequently in the pleura of patients exposed to asbestos. In contrast to many other cancers, relatively few molecular alterations have been described in MMs. The most frequent numerical cytogenetic abnormality in MMs is loss of chromosome 22. The neurofibromatosis type 2 gene (NF2) is a tumor suppressor gene assigned to chromosome 22q which plays an important role in the development of familial and spontaneous tumors of neuroectodermal origin. Although MMs have a different histogenic derivation, the frequent abnormalities of chromosome 22 warranted an investigation of the NF2 gene in these tumors. Both cDNAs from 15 MM cell lines and genomic DNAs from 7 matched primary tumors were analyzed for mutations within the NF2 coding region. NF2 mutations predicting either interstitial in-frame deletions or truncation of the NF2-encoded protein (merlin) were detected in eight cell lines (53%), six of which were confirmed in primary tumor DNAs. In two samples that showed NF2 gene transcript alterations, no genomic DNA mutations were detected, suggesting that aberrant splicing may constitute an additional mechanism for merlin inactivation. These findings implicate NF2 in the oncogenesis of primary MMs and provide evidence that this gene can be involved in the development of tumors other than nervous system neoplasms characteristic of the NF2 disorder. In addition, unlike NF2-related tumors, MM derives from the mesoderm; malignancies of this origin have not previously been associated with frequent alterations of the NF2 gene.

Abstract  The U.S. Navy Asbestos Medical Surveillance Program is a comprehensive effort to decrease exposure to asbestos, a known health hazard. This study was part of a programmatic review of the Asbestos Medical Surveillance Program database, which included 233,353 radiographic examinations from 1990 to 1999. The initial review focused on incidental findings recorded by B-readers for 23,460 radiographs. Abnormalities reported included bullae (0.68%), cancer (0.56%), cardiac size/ shape abnormalities (1.36%), emphysema (0.74%), subpleural fat (2.62%), fractured ribs (1.24%), hilar adenopathy (0.13%), ill-defined diaphragm (0.46%), ill-defined heart border (0.29%), Kerley lines (0.06%), pleural thickening (2.35%), and tuberculosis (0.27%). The rates by age cohort for pleural abnormalities decreased significantly (30-39 years, chi2 for trend = 23.49, df = 1; 40-49 years, chi2 for trend = 176.21; 50-59 years, chi2 for trend = 401.87), but findings were not significantly different for those > or =60 years of age. This suggests that sequential age cohorts in the program are developing fewer pleural abnormalities; pleural abnormalities have historically been associated with asbestos exposure.

Abstract  Studies of human lungs indicate that, for virtually all types of exposure, the relative proportion of amphibole asbestos retained in the lung far exceeds the proportion in the original dust and, conversely, the relative proportion of chrysotile is far less than that in the original dust. Although amphiboles appear to accumulate in lung in proportion to exposure and chrysotile does not, failure of chrysotile deposition is probably not the reason for the disproportionate retention of amphibole fibres. The available data suggest that chrysotile is deposited in the parenchyma but is cleared extremely rapidly, with the vast bulk of fibres removed from human lungs within weeks to months after inhalation; by comparison, amphibole clearance half-lives are of the order of years to decades. The mechanisms of preferential chrysotile clearance remain uncertain, but fragmentation of chrysotile into short fibres, possibly accompanied by extremely rapid dissolution of such fibres, appears to be important in this process. Chrysotile fibres do penetrate to the periphery of the lung, so that differences in mesothelial pathogenicity of chrysotile and amphiboles in regard to mesothelioma are not caused by failure of chrysotile to reach the pleura. The theory that the tremolite contaminant rather than the chrysotile itself is the cause of 'chrysotile-induced' disease (especially mesothelioma) is consistent with the available human data, but the contrary ideas that disease is caused either by the total transient burden of inhaled chrysotile fibres or by a small, sequestered, long-retained fraction of chrysotile fibres still need to be excluded.

Abstract  Mesothelioma is a rare tumor that is considered an asbestos marker disease. It occurs in individuals following a longer latency period from first exposure than other asbestos-related diseases. The tumor also occurs in individuals with a wide range of exposures, including individuals with lower level or secondary exposures. In the present study lung tissue from 54 individuals with a pathological diagnosis of mesothelioma was evaluated for ferruginous body and uncoated asbestos fiber content. The data were compared with an earlier study of mesothelioma cases from the northwestern United States. Tissue was prepared via a digestion procedure, with the collected digestate reviewed by light microscopy for quantification of asbestos bodies and analytical transmission electron microscopy for determination of uncoated fiber burden. Twenty-seven cases in the present study had over 1000 ferruginous bodies per gram of dry tissue. The data suggest that amosite provides a more likely stimulus for ferruginous coating than the other forms of asbestos. All individuals were found to have asbestos fibers in their lung tissue. Amosite was the most commonly found fiber, with anthophyllite being the second most commonly found type of asbestos. The finding of tremolite in the tissue most often was associated with the finding of anthophyllite. A limited number of asbestos fibers of each type would have been seen in the light microscope, with the least detected being chrysotile. The majority of all fiber types were found as short fibers (< 8 mum), although some longer fibers were represented in each type of asbestos. The majority of the individuals were found to have mixed types of asbestos in their lungs.

Abstract  Intriguing helical fibres can be created by self-assembly of simple chiral amphiphilic molecules. We study the parameters governing this spontaneous self-organization by three-dimensional (3D) electron microscopy of the helical fibres embedded in a vitreous ice-matrix. Different stable helices are generated reproducibly using specific combinations of the control parameters in our system. All fibres with diameters less than 25 nm consist of a narrow stack of compartmented bilayers twisted into a left-handed helix. Our novel helical 3D reconstruction procedures in combination with specialized cryomicroscopical specimen preparation, can rapidly elucidate the structure of such helical assemblies. This approach may complement or even replace existing diffraction-based methodologies.

Abstract  The hallmarks of cancer comprise six biological capabilities acquired during the multistep development of human tumors. The hallmarks constitute an organizing principle for rationalizing the complexities of neoplastic disease. They include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. Underlying these hallmarks are genome instability, which generates the genetic diversity that expedites their acquisition, and inflammation, which fosters multiple hallmark functions. Conceptual progress in the last decade has added two emerging hallmarks of potential generality to this list-reprogramming of energy metabolism and evading immune destruction. In addition to cancer cells, tumors exhibit another dimension of complexity: they contain a repertoire of recruited, ostensibly normal cells that contribute to the acquisition of hallmark traits by creating the "tumor microenvironment." Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer.

Abstract  Asbestos inhalation can cause fibrotic reactions both in the lung parenchyma and in the pleura. The incidence and relative proportions of these lesions in any cohort will be dependent on: (1) the time factor: both asbestosis and pleural plaques are progressive diseases and the longer the time from exposure, the more the changes; (2) the dose-response: the more intense the exposure, the earlier and the more advanced is the asbestosis. However, pleural plaques are only moderately dependent on the exposure level and will occur after approximately 30 years in most persons who develop them, even after fairly low exposure; (3) the early lesions are difficult to diagnose radiologically and are prone to overdiagnosis. Considerable caution is necessary when evaluating results if only such lesions are reported. It is generally accepted that the occurrence of radiological asbestosis is a risk factor, particularly for bronchial carcinoma. However, pleural plaques have been considered to be relatively harmless. Recent data have indicated, however, that they can be indicators of sufficient exposure to increase the risk of other asbestos-related diseases, including lung cancer and mesothelioma.

Abstract  To explore associations between exposure to asbestos cement dust and radiographic findings in lung parenchyma and pleura.

Radiographs from 174 blue collar workers and 29 white collar workers from an asbestos cement plant formed one part of the study. Progression of small opacities was further studied in those 124 blue collar workers, for whom two radiographs taken after the end of employment were available. The median readings from five readers who used the full ILO 1980 classification were used. As exposure indices, time since start of employment, duration of employment, cumulative exposure, and average intensity of asbestos exposure were used. The influence of age and smoking was also considered in multiple logistic regression analyses.

Small opacities (profusion > or = 1/0) were closely correlated with time related exposure variables, and showed weaker association with intensity based exposure variables. The odds ratio (OR) for small opacities was equal to 2.8 (90% CI 1.2, 6.7) in the > 30 f(fibre)-y/ml group, compared with those in the 0-10 f-y/ml group. Progression of at least two minor ILO categories after the end of employment was seen in 20%. Also, pleural thickening was closely related to time. By contrast, costophrenic angle obliterations were not associated with the time related variables, but closely associated with the intensity of asbestos exposure, and tended to occur during employment. The OR was 4.5 (90% CI 1.3, 15) in the > 2 f/ml group, compared with those in the 0-1 f/ml group.

In these workers, exposed mainly to chrysotile but also to small amounts of amphibole, the risk of radiographically visible parenchymal abnormality was substantially increased and strongly dependent on time related exposure variables. Progression was found long after the end of exposure. The findings on costophrenic angle obliterations, supposed to be sequelae of benign pleural effusions, were consistent with an immediate reaction triggered by intense asbestos exposure.

Abstract  The objective of this study was to find a model to describe the relationship between the occurrence of pleural plaques and exposure to asbestos. A simple model based on the cumulative exposure was postulated and empirically tested on shipyard workers occupationally exposed to asbestos. Exposure time was used to approximate the cumulative dose. It was found that the incidence of pleural plaques could be described as K(t-w)a where 't' is time since onset of exposure; 'K' is a constant that would depend on the level of asbestos exposure; 'w' is a latency period and was around 13 years; 'a' is a constant that was 0.4. In subgroups of the workers, i.e. plumbers, fitters and platers, 'a' was 0.4, 0.6 and 0.2 respectively.

Abstract  The relationship between the development of mesothelioma and occupational asbestos (1332214) exposure was investigated. A total of 162 hospitals serving 6.5 million people in Pennsylvania reported mesotheliomas diagnosed between 1958 and 1963. There were 34 mesotheliomas of the pleura and 8 of the peritoneum. Of the 15 cases in which lung tissue could be examined, 7 contained asbestos bodies. Of the 42 cases of mesothelioma, 10 had definite occupational exposure to asbestos, 3 were family contacts of asbestos workers, 8 lived in the immediate vicinity of asbestos factories, 6 were clustered around an insulation factory, and 21 had little or no asbestos exposure. Workers exposed to asbestos included makers of acoustic tile and linoleum, plaster and textile workers, and makers of asbestos insulation. The attack rate for mesothelioma was low, and a long latent period existed between exposure and onset of disease. The authors conclude that asbestos may be a causative or trigger agent for malignant mesothelioma in some cases.