RENEB Inter-Laboratory Comparison 2021: Inter-Assay Comparison of Eight Dosimetry Assays.

Tools for radiation exposure reconstruction are required to support the medical management of radiation victims in radiological or nuclear incidents. Different biological and physical dosimetry assays can be used for various exposure scenarios to estimate the dose of ionizing radiation a person has absorbed. Regular validation of the techniques through inter-laboratory comparisons (ILC) is essential to guarantee high quality results. In the current RENEB inter-laboratory comparison, the performance quality of established cytogenetic assays [dicentric chromosome assay (DCA), cytokinesis-block micronucleus assay (CBMN), stable chromosomal translocation assay (FISH) and premature chromosome condensation assay (PCC)] was tested in comparison to molecular biological assays [gamma-H2AX foci (gH2AX), gene expression (GE)] and physical dosimetry-based assays [electron paramagnetic resonance (EPR), optically or thermally stimulated luminescence (LUM)]. Three blinded coded samples (e.g., blood, enamel or mobiles) were exposed to 0, 1.2 or 3.5 Gy X-ray reference doses (240 kVp, 1 Gy/min). These doses roughly correspond to clinically relevant groups of unexposed to low exposed (0-1 Gy), moderately exposed (1-2 Gy, no severe acute health effects expected) and highly exposed individuals (>2 Gy, requiring early intensive medical care). In the frame of the current RENEB inter-laboratory comparison, samples were sent to 86 specialized teams in 46 organizations from 27 nations for dose estimation and identification of three clinically relevant groups. The time for sending early crude reports and more precise reports was documented for each laboratory and assay where possible. The quality of dose estimates was analyzed with three different levels of granularity, 1. by calculating the frequency of correctly reported clinically relevant dose categories, 2. by determining the number of dose estimates within the uncertainty intervals recommended for triage dosimetry (±0.5 Gy or ±1.0 Gy for doses <2.5 Gy or >2.5 Gy), and 3. by calculating the absolute difference (AD) of estimated doses relative to the reference doses. In total, 554 dose estimates were submitted within the 6-week period given before the exercise was closed. For samples processed with the highest priority, earliest dose estimates/categories were reported within 5-10 h of receipt for GE, gH2AX, LUM, EPR, 2-3 days for DCA, CBMN and within 6-7 days for the FISH assay. For the unirradiated control sample, the categorization in the correct clinically relevant group (0-1 Gy) as well as the allocation to the triage uncertainty interval was, with the exception of a few outliers, successfully performed for all assays. For the 3.5 Gy sample the percentage of correct classifications to the clinically relevant group (≥2 Gy) was between 89-100% for all assays, with the exception of gH2AX. For the 1.2 Gy sample, an exact allocation to the clinically relevant group was more difficult and 0-50% or 0-48% of the estimates were wrongly classified into the lowest or highest dose categories, respectively. For the irradiated samples, the correct allocation to the triage uncertainty intervals varied considerably between assays for the 1.2 Gy (29-76%) and 3.5 Gy (17-100%) samples. While a systematic shift towards higher doses was observed for the cytogenetic-based assays, extreme outliers exceeding the reference doses 2-6 fold were observed for EPR, FISH and GE assays. These outliers were related to a particular material examined (tooth enamel for EPR assay, reported as kerma in enamel, but when converted into the proper quantity, i.e. to kerma in air, expected dose estimates could be recalculated in most cases), the level of experience of the teams (FISH) and methodological uncertainties (GE). This was the first RENEB ILC where everything, from blood sampling to irradiation and shipment of the samples, was organized and realized at the same institution, for several biological and physical retrospective dosimetry assays. Almost all assays appeared comparably applicable for the identification of unexposed and highly exposed individuals and the allocation of medical relevant groups, with the latter requiring medical support for the acute radiation scenario simulated in this exercise. However, extreme outliers or a systematic shift of dose estimates have been observed for some assays. Possible reasons will be discussed in the assay specific papers of this special issue. In summary, this ILC clearly demonstrates the need to conduct regular exercises to identify research needs, but also to identify technical problems and to optimize the design of future ILCs.

RENEB Inter-Laboratory Comparison 2021: The Dicentric Chromosome Assay.

After large-scale radiation accidents where many individuals are suspected to be exposed to ionizing radiation, biological and physical retrospective dosimetry assays are important tools to aid clinical decision making by categorizing individuals into unexposed/minimally, moderately or highly exposed groups. Quality-controlled inter-laboratory comparisons of simulated accident scenarios are regularly performed in the frame of the European legal association RENEB (Running the European Network of Biological and Physical retrospective Dosimetry) to optimize international networking and emergency readiness in case of large-scale radiation events. In total 33 laboratories from 22 countries around the world participated in the current RENEB inter-laboratory comparison 2021 for the dicentric chromosome assay. Blood was irradiated in vitro with X rays (240 kVp, 13 mA, ∼75 keV, 1 Gy/min) to simulate an acute, homogeneous whole-body exposure. Three blood samples (no. 1: 0 Gy, no. 2: 1.2 Gy, no. 3: 3.5 Gy) were sent to each participant and the task was to culture samples, to prepare slides and to assess radiation doses based on the observed dicentric yields from 50 manually or 150 semi-automatically scored metaphases (triage mode scoring). Approximately two-thirds of the participants applied calibration curves from irradiations with γ rays and about 1/3 from irradiations with X rays with varying energies. The categorization of the samples in clinically relevant groups corresponding to individuals that were unexposed/minimally (0-1 Gy), moderately (1-2 Gy) or highly exposed (>2 Gy) was successfully performed by all participants for sample no. 1 and no. 3 and by ≥74% for sample no. 2. However, while most participants estimated a dose of exactly 0 Gy for the sham-irradiated sample, the precise dose estimates of the samples irradiated with doses >0 Gy were systematically higher than the corresponding reference doses and showed a median deviation of 0.5 Gy (sample no. 2) and 0.95 Gy (sample no. 3) for manual scoring. By converting doses estimated based on γ-ray calibration curves to X-ray doses of a comparable mean photon energy as used in this exercise, the median deviation decreased to 0.27 Gy (sample no. 2) and 0.6 Gy (sample no. 3). The main aim of biological dosimetry in the case of a large-scale event is the categorization of individuals into clinically relevant groups, to aid clinical decision making. This task was successfully performed by all participants for the 0 Gy and 3.5 Gy samples and by 74% (manual scoring) and 80% (semiautomatic scoring) for the 1.2 Gy sample. Due to the accuracy of the dicentric chromosome assay and the high number of participating laboratories, a systematic shift of the dose estimates could be revealed. Differences in radiation quality (X ray vs. γ ray) between the test samples and the applied dose effect curves can partly explain the systematic shift. There might be several additional reasons for the observed bias (e.g., donor effects, transport, experimental conditions or the irradiation setup) and the analysis of these reasons provides great opportunities for future research. The participation of laboratories from countries around the world gave the opportunity to compare the results on an international level.

Coherently-averaged dual comb spectrometer at 7.7†µm with master and follower quantum cascade lasers.

We demonstrate coherent averaging of the multi-heterodyne beat signal between two quantum cascade laser frequency combs in a master-follower configuration. The two combs are mutually locked by acting on the drive current to control their relative offset frequency and by radio-frequency extraction and injection locking of their intermode beat signal to stabilize their mode spacing difference. By implementing an analog common-noise subtraction scheme, a reduction of the linewidth of all heterodyne beat notes by five orders of magnitude is achieved compared to the free-running lasers. We compare stabilization and post-processing corrections in terms of amplitude noise. While they give similar performances in terms of signal-to-noise ratio, real-time processing of the stabilized signal is less demanding in terms of computational power. Lastly, a proof-of-principle spectroscopic measurement was performed, showing the possibility to reduce the amount of data to be processed by three orders of magnitude, compared to the free-running system.

Maternal occupational exposures to nanoscale particles and small for gestational age outcome in the French Longitudinal Study of Children.

OBJECTIVES: To investigate the association between maternal occupational exposures to nanoscale particles (NPs) during pregnancy and small for gestational age (SGA). METHODS: This study included 11,224 mothers and singleton birth pairs from the French Longitudinal Study of Children (ELFE cohort), which included infants born after 33 weeks of gestation or more in continental France in 2011. Mothers who did not work during pregnancy were excluded from the analyses. Maternal occupational exposures to NPs was estimated using a job-exposure matrix for the probability (>50%: occupationally exposed group, n = 569; 0%: occupationally non-exposed group, n = 9113; between these two thresholds: uncertain group, n = 1542) and frequency of exposure. Associations were estimated from multivariate logistic regression models for occupationally exposed vs occupationally unexposed groups in a first analysis, and with the frequency-weighted duration of work for the occupationally exposed group only in a second analysis. RESULTS: Among working mothers, 5.1% were occupationally exposed to NPs. Maternal occupational exposures to NPs was associated with SGA (ORa = 1.63, 95% CI: 1.22, 2.18). The frequency-weighted duration of work for the occupationally exposed group (n = 569) was not associated with SGA (ORa = 1.02, 95% CI: 0.97, 1.08) in adjusted analyses. CONCLUSIONS: These results, showing a significant association between occupational exposures to NPs and SGA, should encourage further studies to examine the adverse effect of NPs exposure on fetal development.

Frequency comb metrology with an optical parametric oscillator.

We report on the first demonstration of absolute frequency comb metrology with an optical parametric oscillator (OPO) frequency comb. The synchronously-pumped OPO operated in the 1.5-µm spectral region and was referenced to an H-maser atomic clock. Using different techniques, we thoroughly characterized the frequency noise power spectral density (PSD) of the repetition rate frep, of the carrier-envelope offset frequency fCEO, and of an optical comb line νN. The comb mode optical linewidth at 1557 nm was determined to be ~70 kHz for an observation time of 1 s from the measured frequency noise PSD, and was limited by the stability of the microwave frequency standard available for the stabilization of the comb repetition rate. We achieved a tight lock of the carrier envelope offset frequency with only ~300 mrad residual integrated phase noise, which makes its contribution to the optical linewidth negligible. The OPO comb was used to measure the absolute optical frequency of a near-infrared laser whose second-harmonic component was locked to the F = 2→3 transition of the 87Rb D2 line at 780 nm, leading to a measured transition frequency of νRb = 384,228,115,346 ± 16 kHz. We performed the same measurement with a commercial fiber-laser comb operating in the 1.5-µm region. Both the OPO comb and the commercial fiber comb achieved similar performance. The measurement accuracy was limited by interferometric noise in the fibered setup of the Rb-stabilized laser.

[Occupational risk factors for lung cancer]. / Facteurs de risque professionnels du cancer bronchopulmonaire.

OBJECTIVE: We aimed to review the literature regarding the dose-response relationship between occupational exposure to chemicals classified by the International Agency for Research on Cancer (IARC) as carcinogenic agents and the risk of some lung cancers and on any combined effect with tobacco exposure on lung cancer risk. METHODS: A literature search was performed in three databases as well as in the IARC monographs between January 1990 and April 2015. RESULTS: The literature is abundant for some carcinogens such as asbestos, crystalline silica and diesel exhaust fumes but is more sparse for many carcinogens and particularly any interaction with tobacco on lung cancer risk. CONCLUSION: Few data exist for most lung occupational carcinogens including their interaction with tobacco exposure. In the case of exposure to occupational carcinogens and co-exposure to tobacco smoke, there is a dual primary prevention objective: the elimination of both occupational risk factors and tobacco smoke.

[The French mesothelioma network from 1998 to 2013]. / Mésothéliome: les dispositifs en place en France « le réseau mésothéliome ¼ 1998-2013.

Mesothelioma is a rare disease less than 0.3% of cancers in France, very aggressive and resistant to the majority of conventional therapies. Asbestos exposure is nearly the only recognized cause of mesothelioma in men observed in 80% of case. In 1990, the projections based on mortality predicted a raise of incidence in mesothelioma for the next three decades. Nowadays, the diagnosis of this cancer is based on pathology, but the histological presentation frequently heterogeneous, is responsible for numerous pitfalls and major problems of early detection toward effective therapy. Facing such a diagnostic, epidemiological and medico-legal context, a national and international multidisciplinary network has been progressively set up in order to answer to epidemiological survey, translational or academic research questions. Moreover, in response to the action of the French Cancer Program (action 23.1) a network of pathologists was organized for expert pathological second opinion using a standardized procedure of certification for mesothelioma diagnosis. We describe the network organization and show the results during this last 15years period of time from 1998-2013. These results show the major impact on patient's management, and confirm the interest of this second opinion to provide accuracy of epidemiological data, quality of medico-legal acknowledgement and accuracy of clinical diagnostic for the benefit of patients. We also show the impact of these collaborative efforts for creating a high quality clinicobiological, epidemiological and therapeutic data collection for improvement of the knowledge of this dramatic disease.

Occupational and non-occupational attributable risk of asbestos exposure for malignant pleural mesothelioma.

OBJECTIVES: To estimate the proportion of pleural mesothelioma cases that can be attributed to asbestos exposure in France including non-occupational exposure. METHODS: A population-based case-control study including 437 incident cases and 874 controls was conducted from 1998 to 2002. Occupational and non-occupational asbestos exposure was assessed retrospectively by two expert hygienists. ORs of pleural mesothelioma for asbestos-exposed subjects compared to non-exposed subjects, and population-attributable risk (ARp) of asbestos exposure were estimated using a conditional logistic regression. RESULTS: A clear dose-response relationship was observed between occupational asbestos exposure and pleural mesothelioma (OR=4.0 (99% CI 1.9 to 8.3) for men exposed at less than 0.1 f/mL-year vs. 67.0 (99% CI 25.6 to 175.1) for men exposed at more than 10 f/mL-year). The occupational asbestos ARp was 83.1% (99% CI 74.5% to 91.7%) for men and 41.7% (99% CI 25.3% to 58.0%) for women. A higher risk of pleural mesothelioma was observed in subjects non-occupationally exposed to asbestos compared to those never exposed. The non-occupational asbestos ARp for these subjects was 20.0% (99% CI -33.5% to 73.5%) in men and 38.7% (99% CI 8.4% to 69.0%) in women. When considering all kinds of asbestos exposure, ARp was 87.3% (99% CI 78.9% to 95.7%) for men and 64.8% (99% CI 45.4% to 84.3%) for women. CONCLUSIONS: Our study suggests that the overall ARp in women is largely driven by non-occupational asbestos exposure arguing for the strong impact of such exposure in pleural mesothelioma occurrence. Considering the difficulty in assessing domestic or environmental asbestos exposure, this could explain the observed difference in ARp between men and women.

[Compensation for occupational diseases after tomodensitometry screening for benign pleuro-pulmonary disease in a multiregional post-occupational medical surveillance program of asbestos-exposed retired workers]. / Déclaration et reconnaissance en maladie professionnelle après dépistage tomodensitométrique de maladies pleuropulmonaires bénignes dans le programme multirégional de surveillance postprofessionnelle de personnes exposées à l'amiante.

BACKGROUND: Underreporting of occupational diseases related to asbestos exposure remains a matter of concern in France. The aim of this study was to evaluate the number of claims for compensation for asbestos-related non-malignant pulmonary or pleural occupational disease in subjects having undergone a chest CT-scan in a multiregional screening programme. METHODS: Among the 5444 voluntary retired asbestos-exposed subjects recruited in four regions between 2003 and 2005 who had undergone a chest CT-scan, the number of claims for compensation for an asbestos-related pulmonary or pleural benign disease was analysed in 2006 and 2010. RESULTS: Following CT-scan screening, 17.2% of participants were acknowledged as presenting with an asbestos-related non-malignant occupational disease, essentially pleural plaques, by the French National Health Insurance fund. Underreporting decreased as duration of follow-up after CT-scan increased. Nevertheless, 4 years after CT-scan, underreporting was still as high as 36% for subjects identified as presenting with pleural plaques. Mean duration between the date of CT-scan and the date of recognition as occupational disease was 7.4 months, shorter in cases where screening was coordinated by specialized centres. CONCLUSION: A plan of action for an easier claiming process for compensation of asbestos-related diseases is desired. This could probably be obtained through improved sensitization of physicians engaged in the follow-up of asbestos-exposed subjects, and by standardization of the interpretation and reporting of asbestos-related abnormalities observed on chest CT-scans.

[Chronic central nervous system effects of pesticides: state-of-the-art]. / Effets chroniques des pesticides sur le système nerveux central : état des connaissances épidémiologiques.

BACKGROUND: Given the neurotoxic properties of pesticides, suggested by experimental results and clinical observations, many epidemiological studies have investigated neurological effects following acute or chronic exposure to pesticides. This review provides an overview of current knowledge about pesticide effects on the central nervous system: neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis), cognitive disorders, and psychiatric disorders (mood disorders, anxiety, depression and suicide). RESULTS: Parkinson's disease, the most widely studied in relation with pesticide exposure, particularly with insecticides and herbicides, was observed to be a risk factor of the disease. Evidence is scarce for Alzheimer's disease and amyotrophic lateral sclerosis, but quite consistent. Cognitive and psychiatric disorders were often observed in relation with organophosphate insecticide exposure. Cognitive disorders were found associated with acute and chronic exposures, and psychiatric disorders mostly with poisonings. These epidemiologic studies were limited by a lack of detailed and reliable exposure assessment. The role of genetic susceptibilities has been recently observed, but must be further investigated.

Returning to work after a stroke: a retrospective study at the Physical and Rehabilitation Medicine Center La Tour de Gassies.

OBJECTIVE: To study work re-entry by patients having suffered a stroke at least 3 years previously. PATIENTS AND METHODS: This was a retrospective survey in which a questionnaire was administered to all patients admitted after a first stroke to the "La Tour de Gassies" Centre for Physical and Rehabilitation Medicine (CPRM) in France between January 2005 and June 2007 and who were in work at the time of the incident. RESULTS: Fifty-six of the 72 included patients (78%) completed and returned the survey questionnaire. The mean age at the time of the stroke was 48.3±10.1. Eighteen (32.1%) of the 56 patients returned to work after their stroke (mean post-stroke time interval: 19.2±13.4 months). Negative prognostic factors for a return to work were living alone, the presence of severe functional impairment and the presence of speech disorders. Positive prognostic factors included specific, professional support and early involvement of the occupational physician. Patients who resumed driving were more likely to return to work and there was a positive correlation between the time to work re-entry and the time to resumption of driving. CONCLUSION: Close cooperation between occupational health services and CPRM appears to be necessary to speed the return to work by stroke patients.

Pulmonary nodules detected by thoracic computed tomography scan after exposure to asbestos: diagnostic significance.

OBJECTIVE: To analyse the relationship between pulmonary nodules detected by radiologists using computed tomography and cumulative exposure to asbestos or asbestos-related pleuro-pulmonary diseases in 5662 asbestos-exposed subjects, and the relationship between pulmonary nodules and thoracic cancer, to determine whether a specific surveillance strategy based on cumulative asbestos exposure should be adopted. DESIGN: Standardised incidence and mortality ratios (SIR) for lung cancer and pleural mesothelioma were calculated in patients with and without mention of pulmonary nodules and compared using comparative morbidity figures. RESULTS: A significant excess incidence of primary lung cancer and pleural mesothelioma was observed among subjects presenting with pulmonary nodule(s) (SIR respectively 1.95, 95%CI 1.22-2.95, and 11.88, 95%CI 3.20-30.41). However, there was no significant relationship between pulmonary nodules mentioned by radiologists and cumulative asbestos exposure or between pulmonary nodules and the presence of asbestos-related benign diseases. CONCLUSIONS: This study confirms the expected excess prevalence of lung cancer in subjects presenting with pulmonary nodules according to the radiologist's report, and shows the absence of relationship between the presence of nodules and level of cumulative asbestos exposure. Our study therefore offers no argument in favour of specific surveillance modalities based on estimated cumulative asbestos exposure.

Respiratory effects of manufactured nanoparticles.

Nanotechnology is the set of techniques used to engineer, characterize, and produce materials that have at least one dimension within the nanoscale. These nanomaterials, or nanoobjects, include nanoparticles and nanotubes. As dictated by the laws of quantum physics, a size within the nanoscale results in unique physicochemical properties and distinctive behaviors. Nanotechnology has a host of applications in fields ranging from cosmetology to the industry and medicine. The production and use of nanomaterials are expanding at a brisk pace. However, concerns are emerging about the potential health effects of nanoparticles in the short and long terms. These concerns are rooted in data on the harmful health effects of micrometric airborne particulate matter. Conceivably, these adverse effects might be amplified when the particles are within the nanoscale. This article is a nonexhaustive overview of current data on the penetration, deposition, translocation, and elimination of inhaled nanoparticles and on the respiratory effects of metallic nanoparticles (with special attention to titanium dioxide) and carbon nanotubes. Both in vivo and in vitro studies consistently found biological effects of nanoparticles on the respiratory system, including oxidative stress generation, proinflammatory and prothrombotic effects, pulmonary fibrosis and emphysema, and DNA damage. Improved knowledge of the potential biological effects of nanoparticles is needed to guide preventive strategies for the workplace and/or general population if needed.

Asbestos-related cancer risk in patients with asbestosis or pleural plaques.

INTRODUCTION: The relationships between benign asbestos-related diseases (asbestosis and pleural plaques) and thoracic cancers are still debated. The aim of this paper was to review the epidemiological data relevant to this issue. CURRENT KNOWLEDGE: Published studies show a significant relationship between occupational exposure to asbestos and lung cancer risk, even in the absence of abnormalities consistent with asbestosis on the postero-anterior chest x-ray. For a given cumulative asbestos exposure, the presence of radiographic evidence of asbestosis is associated with an increased risk of lung cancer. Among asbestos-exposed individuals, those having radiographic evidence of pleural plaques are at increased risk for lung cancer and pleural mesothelioma, compared to the general population. However, there is no evidence that pleural plaque confers an increased risk of lung cancer or pleural mesothelioma within a population of individuals having the same cumulative asbestos exposure. PERSPECTIVES: The studies identified for this review relied only on chest radiograph data. Studies involving accurate evaluations of asbestos exposure and computed tomography of the chest are needed. CONCLUSION: Currently available data indicate that patient follow-up modalities should be dictated solely by the estimated cumulative asbestos exposure and not by the existence of pleural plaques.

[Exposure to asbestos and the indoor environment]. / Situations d'exposition à l'amiante et environnement intérieur.

A link between the inhalation of asbestos fibres and the outcome of benign and malignant respiratory diseases has been established from numerous epidemiological data in occupational settings. Occupational exposure limit values have been established with a gradual lowering of these over time. Conversely, there are few epidemiological data dealing with exposure in the indoor environment. However, numerous materials and products containing asbestos (MPCA) are present in the indoor environment, due to their widespread use in the construction sector in the years between 1960 and 1990. The regulations were changed from the late 1990s, leading to a systematic inventory of the presence of asbestos-containing materials in buildings. The aim of this manuscript is to clarify the different types of MPCA encountered in the indoor environment, to describe the techniques used to highlight asbestos depending on the nature of the materials, the regulatory requirements relating to asbestos in non-occupational situations, and to update on the state of knowledge on asbestos-related diseases in the indoor environment.

Evolution of pleural cancers and malignant pleural mesothelioma incidence in France between 1980 and 2005.

The evolution of pleural cancers and malignant pleural mesothelioma incidence in France between 1980 and 2005 was analysed using data derived from the French network of cancer registries (FRANCIM) and the French National Mesothelioma Surveillance Program (PNSM). Mesothelioma proportions in pleural cancers were calculated by diagnosis year in the 1980-2000 period. Our results suggest that the incidences of pleural cancer and mesothelioma levelled off in French men since 2000 and continued to increase in French women. A decrease of the annual pleural cancer incidence average in men was noticed (-3.4% of annual rate of change) between 2000 and 2005. The proportion of pleural cancers that were mesothelioma was unchanged between 1980 and 2003 with an average of 86%. The age standardised incidence rate of pleural mesothelioma remained relatively stable between 1998 and 2005 with a slight falling trend. For women, the age standardised incidence rate of pleural cancers and mesothelioma increased during the period 1998-2005. Additionally, the proportion of pleural cancers that were mesothelioma increased during the same period of time. Finally, the increased trend observed in the incidence of pleural mesothelioma and cancers in women is credibly due to their under diagnosis in the 1980-1997 period. The comparison between the French incidence and the American and British ones shows that the decreasing trend in incidence of mesothelioma and pleural cancers in French men since 2000 is potentially associated with a lower amphibole consumption and by the implementation of safety regulations at work from 1977.

[Respiratory effects of manufactured nanoparticles]. / Effets respiratoires des nanoparticules manufacturées.

Nanotechnology, defined as techniques aimed to design, characterize and produce materials on a nanometer scale, is a fast-growing field today. Nanomaterials are made of nanoobjects (nanoparticles, nanofibers, nanotubes...). The nanoscale confers on these materials their novel, hitherto unknown, chemical and physical properties by the laws of quantum physics which are essentially expressed on this scale. Nanotechnology applications are numerous (e.g., cosmetics, industry and medicine) and they keep growing. We can safely predict that the production and utilization of nanomaterials will increase greatly in the years to come. Nonetheless, the same properties that make these nanomaterials very attractive are a source of concern: there are questions about their potential toxicity, their long-term side effects, and their biodegradability. These questions are based on knowledge of the toxic effects of micrometric particles in air pollution and the fear that these effects will be amplified because of the nanometric size of the new materials. We present in this article a global but not exhaustive summary of current knowledge. We begin by defining lung penetration, deposition, translocation and elimination of nanoparticles. Finally, we consider the respiratory effects of metallic nanoparticles, titanium dioxide nanoparticles in particular, and carbon nanotubes. In vivo and in vitro experimental studies currently available highlight the existence of biological effects of nanoparticles on the respiratory system with generation of oxidative stress, pro-inflammatory and pro-thrombotic effects and the possible development of fibrosis and pulmonary emphysema or DNA damage. A better understanding of the potential biological effects of nanoparticles is required to implement appropriate preventive measures in the workplace and/or in the general population, if this should be necessary.

[Asbestos-related cancer risk in the presence of asbestosis or pleural plaques]. / Risque de cancer lié à l'amiante en présence d'asbestose ou de plaques pleurales.

INTRODUCTION: The relationships between benign asbestos-related diseases (asbestosis and pleural plaques) and thoracic cancers are still debated. The aim of this paper is to analyse epidemiological data which investigate this topic. STATE OF THE ART: Published studies show that there is a significant relationship between occupational exposure to asbestos and lung cancer risk, even in the absence of abnormalities consistent with asbestos exposure on postero-anterior chest x-ray. In subjects with occupational exposure to asbestos, an increased risk of lung cancer and pleural mesothelioma is observed in subjects with pleural plaques on chest x-ray, in comparison with the general population. In exposed subjects with similar cumulative exposure to asbestos, it is not demonstrated that pleural plaques are associated with an increased risk of lung cancer or pleural mesothelioma. PERSPECTIVES: All the analysed studies are only based on radiographic data. Their results must be confirmed by additional studies including a rigorous evaluation of the cumulative exposure to asbestos and chest CT-scans. CONCLUSION: In the present state of knowledge, isolated pleural plaques do not justify specific medical surveillance, as compared to that required by the mere estimated cumulative exposure to asbestos.

Pleural plaques and asbestosis: dose- and time-response relationships based on HRCT data.

Most studies on asbestos-related diseases are based on chest radiographs, and dose-response relationships are still controversial. The aim of this study was to describe the most relevant parameters of asbestos exposure linked to pleural plaques and asbestosis diagnosed by high-resolution computed tomography (HRCT). A large screening programme including systematic HRCT examinations was organised from 2003 to 2005 in France for formerly asbestos-exposed workers. The time since first exposure (TSFE), level, duration and cumulative exposure to asbestos were used in adjusted unconditional logistic regression to model the relationships of the two diseases. Analysis of a population of 5,545 subjects demonstrated that TSFE (p<0.0001) and cumulative exposure (p = 0.02) (or level, depending on the models used), were independently associated with the frequency of pleural plaques. Only cumulative exposure (p<0.0001) or level of exposure (p = 0.02) were significantly associated with asbestosis. All trend tests were significant for these parameters. To date and to our knowledge, this study is the largest programme based on HRCT for the screening of asbestos-exposed subjects. Both time-response and dose-response relationships were demonstrated for pleural plaques, while only dose-response relationships were demonstrated for asbestosis. These parameters must be included in the definition of high-risk populations for HRCT-based screening programmes.