Perspectives in Biological Monitoring of Inhaled Nanosized Particles.

Given the results of experimental studies, occupational or environmental exposures to manufactured nanoparticles or to unintentionally produced ultrafine particles may result in health effects or diseases in humans. In this review, we synthesize published data of experimental studies on the distribution of inhaled nanoparticles and the first case reports to discuss the potential usefulness of their biological monitoring for clinical purposes. Toxicokinetic studies suggest that nanoparticles may be absorbed predominantly by respiratory and oral routes with possible systemic translocation, leading to accumulation in the peripheral organs or excretion in feces or urine. Some methods used in these studies may be applied successfully in retrospective evaluation of exposure or in follow-up of occupational exposure in the workplace. Biological monitoring of nanoparticles should be based on imaging methods that are essential to confirm their presence and to characterize them in tissue associated with analytical quantitative methods. The first case reports reviewed emphasize the urgent need for the development of standardized procedures for the preparation and analysis of biological samples with a view to characterizing and quantifying nanoparticles.

Quantification of short and long asbestos fibers to assess asbestos exposure: a review of fiber size toxicity.

The fibrogenicity and carcinogenicity of asbestos fibers are dependent on several fiber parameters including fiber dimensions. Based on the WHO (World Health Organization) definition, the current regulations focalise on long asbestos fibers (LAF) (Length: L ≥ 5 µm, Diameter: D < 3 µm and L/D ratio > 3). However air samples contain short asbestos fibers (SAF) (L < 5 µm). In a recent study we found that several air samples collected in buildings with asbestos containing materials (ACM) were composed only of SAF, sometimes in a concentration of ≥10 fibers.L-1. This exhaustive review focuses on available information from peer-review publications on the size-dependent pathogenetic effects of asbestos fibers reported in experimental in vivo and in vitro studies. In the literature, the findings that SAF are less pathogenic than LAF are based on experiments where a cut-off of 5 µm was generally made to differentiate short from long asbestos fibers. Nevertheless, the value of 5 µm as the limit for length is not based on scientific evidence, but is a limit for comparative analyses. From this review, it is clear that the pathogenicity of SAF cannot be completely ruled out, especially in high exposure situations. Therefore, the presence of SAF in air samples appears as an indicator of the degradation of ACM and inclusion of their systematic search should be considered in the regulation. Measurement of these fibers in air samples will then make it possible to identify pollution and anticipate health risk.

High risk of malignant mesothelioma and pleural plaques in subjects born close to ophiolites.

BACKGROUND: Ophiolites, a special sequence of geologic rock units, are known sources of naturally occurring asbestos. The aim of this study was to test whether the occurrence of malignant mesothelioma (MM) or pleural plaques (PPs) in the province of Sivas, Turkey, is determined by the proximity of the patient's birthplace to ophiolites and, if so, to establish the magnitude of the risk. METHODS: The birthplaces of patients with MM or PPs (cases) and patients with prostate or breast cancer (control subjects), diagnosed between 2000 and 2010 and identified through a mandatory cancer registry or from hospital records (PPs), were located on a geologic map, and the nearest distance to ophiolites was measured. The relation of MM or PPs with distance to ophiolites was analyzed by logistic regression. Samples of soil and house plaster were determined by x-ray diffraction. RESULTS: Patients with MM (n = 100) or PPs (n = 133) were born significantly nearer to ophiolites (median distance, 4.5 km for men, 0 km for women) than were patients with prostate cancer (n = 161) or breast cancer (n = 139) (median distance, 20 km for both). ORs were 1.6 (men) ( P < .001) and 2.0 (women) ( P < .001) for every 5-km decrease in the distance of birthplace to ophiolites for MM, compared with prostate and breast cancer, respectively. CONCLUSION: In this area without substantial industrial asbestos use, there is an association between the occurrence of mesothelioma (and of PPs) and the proximity of the subject's birthplace to ophiolites.

Clinical, histopathological and mineralogical analysis findings of an unusual case of pneumoconiosis.

A 43-year-old man with a long history of dyspnea which had progressively worsened over the preceding month is presented. He had worked in an antimony mine for 3 years. Radiologically, there were diffuse reticulonodular shadowing opacities in both lung parenchymas. Histopathologic examination of the open-lung biopsy specimen revealed alveolar spaces filled with dust-laden macrophages and amorphous proteinaceous semifluid, the latter being immunoreactive for Human Surfactant Apoprotein A, associated with marked interstitial accumulation of the similar-looking macrophages along the bronchovascular bundles and mild interstitial fibrosis. Silicotic nodules or mixed dust fibrosis were not seen. The patient was diagnosed as silicoproteinosis with unusual histopathological features because he had worked in an antimony mine for only 3 years and had 86% silica in a mineralogical analysis. Pneumoconiosis is a rare lung disease which may be confused with other interstitial lung diseases. Clinical, radiological and unusual histopathologic features of this rare case are presented and discussed with the differential diagnosis, especially of mixed dust pneumoconiosis.

Asbestos exposure during uncontrolled removal of sprayed-on asbestos.

Asbestos-containing materials in place in buildings, especially sprayed-on asbestos, are still an important health threat. Clearance of these materials has to be operated by specifically trained workers wearing specific individual protection suits after containment of the contaminated area. Good work practices are, however, not always applied. We report the case of two workers hired for ∼1 week to remove sprayed-on amosite asbestos during the remodeling of a former industrial hall. Regulatory protective equipments were not used. A legal action was initiated after disclosure of the working conditions. Medical examinations were performed 18 and 22 months after exposure. Workers denied any other asbestos exposure. Lung function tests and chest computed tomography scans were normal. Very high levels of asbestos fibers and bodies were discovered on mineralogical analysis of bronchoalveolar lavage fluid (BALF) by phase contrast light microscopy and analytical electron microscopy. All fibers were amosite. An extrapolation considering duration of exposure, breathing pattern, and BALF fiber content suggests that the workers were exposed to airborne fiber concentrations in the range from several tens to about a hundred World Health Organization fibers per milliliter air. In conclusion, exposures to historical airborne fiber levels prevailing half a century ago may still occur today when the work regulations are not applied. In these conditions, even very short exposures may result in considerable lung fiber retention in case of amphibole exposure with the subsequent risk for developing asbestos-related diseases. Fiber analysis in BALF is useful to clarify such exposures.

Endemic malignant mesothelioma: exposure to erionite is more important than genetic factors.

The village of Karain, Turkey, has the world's highest prevalence rate of malignant mesothelioma (MM). Environmental exposure to erionite is thought to cause the disease. However, it has also been suggested that the disease is mainly genetic. Residents in Karain village were traced from 1990 to 2006. Mineral samples were obtained from stones used in construction of their houses and any fibers present were identified. All women who had moved to the village as brides were traced and their cause of death determined. MM was the cause of death in 52 of 322 villagers, representing 50.5% of all deaths. Only 2 of 8 types of stones used in construction contained erionite, and these stones had been used almost exclusively in the mid-sections of the village, where MM was common. In houses not containing erionite, no cases of MM were observed. Sixty-four women came as brides to Karain from villages where erionite or asbestos is not found. Of the 16 women who have died, 11 (69%) died from MM. The extreme risk of MM in Karain is due to indoor exposure to erionite. The effect of genetic factors on mesothelioma development cannot be evaluated in this study, but is likely to be minor.

Proposed criteria for mixed-dust pneumoconiosis: definition, descriptions, and guidelines for pathologic diagnosis and clinical correlation.

We defined mixed-dust pneumoconiosis (MDP) pathologically as a pneumoconiosis showing dust macules or mixed-dust fibrotic nodules (MDF), with or without silicotic nodules (SN), in an individual with a history of exposure to mixed dust. We defined the latter arbitrarily as a mixture of crystalline silica and nonfibrous silicates. According to our definition of MDP, therefore, MDF should outnumber SN in the lung to make a pathologic diagnosis of MDP. In the absence of confirmation of exposure, mineralogic analyses can be used to support the pathologic diagnosis. The clinical diagnosis of MDP requires the exclusion of other well-defined pneumoconioses, including asbestosis, coal workers' pneumoconiosis, silicosis, hematite miners' pneumoconiosis, welders' pneumoconiosis, berylliosis, hard metal disease, silicate pneumoconiosis, diatomaceous earth pneumoconiosis, carborundum pneumoconiosis, and corundum pneumoconiosis. Typical occupations associated with the diagnosis of MDP include metal miners, quarry workers, foundry workers, pottery and ceramics workers, and stonemasons. Irregular opacities are the major radiographic findings in MDP (ILO 1980), in contrast to silicosis, in which small rounded opacities predominate. Clinical symptoms of MDP are nonspecific. MDP must be distinguished from a variety of nonoccupational interstitial pulmonary disorders.

'Black Spots' and hyaline pleural plaques on the parietal pleura of 150 urban necropsy cases.

The absence of any direct connection between the lung and the parietal pleura raises questions about the mechanisms of pleural migration and retention of inhaled particles. It has been suggested that specific areas of parietal pleura absorb and retain inorganic particles from the pleural space, including carbon pigments and asbestos fibers, and could be starting points for pathologic changes induced by mineral fibers. These particle-collecting structures have been called "black spots." To study their distribution, macroscopic appearance, and possible relationship with pleural plaques, the parietal pleura of 150 consecutive necropsies of urban dwellers (mean age 67.7 +/- 12.9 years) were examined. The size and intensity of spots were scored and recorded on a computer scheme together with information of the presence of pleural plaques. Black spots were observed in 92.7% of the cases. They were mainly located in the lower costal and diaphragmatic zones and could correspond to the anatomic distribution of structures involved in pleural cavity clearance. Scores correlated with sex and age. There was no relationship between the predominant locations of black spots and hyaline pleural plaques.