Occupational asbestos exposure and ovarian cancer: updated systematic review.

BACKGROUND: The association between asbestos exposure and ovarian cancer has been questioned given the possible misdiagnosis of peritoneal mesothelioma as ovarian cancer. AIMS: To update a systematic review on ovarian cancer risk in women occupationally exposed to asbestos, exploring the association with the time since first exposure and the duration of exposure. METHODS: We searched PubMed from 2008 onwards, screened previous systematic reviews, combined standardized mortality ratios (SMR) using random effect models and quantified heterogeneity using the I2 statistic. To assess tumour misclassification, we compared the distribution of observed excess ovarian cancers (OEOC) to that expected (EEOC) from the distribution of peritoneal cancers in strata of latency and exposure duration. RESULTS: Eighteen publications (20 populations), including a pooled analysis of 21 cohorts, were included. The pooled SMR was 1.79 (95% confidence interval 1.38-2.31), with moderate heterogeneity between studies (I2 = 42%), based on 144 ovarian cancer deaths/cases. The risk was increased for women with indirect indicators of higher exposure, longer duration and latency, and lower for chrysotile than for crocidolite exposure. The effect of duration and latency could not be completely disentangled, since no multivariate analysis was available for time-related variables. The dissimilarity index between OEOC and EEOC for the time since first exposure was small suggesting a similar pattern of risk. CONCLUSIONS: While some misclassification between ovarian and peritoneal cancers cannot be excluded, the observed excess risk of ovarian cancer should be added to the overall disease burden of asbestos.

A comparison between the effects of over-expression of miRNA-16 and miRNA-34a on cell cycle progression of mesothelioma cell lines and on their cisplatin sensitivity.

The prognosis of patients affected by malignant pleural mesothelioma (MPM) is presently poor and no therapeutic strategies have improved their survival yet. Introduction of miRNA mimics to restore their reduced or absent functionality in cancer cells is considered an important opportunity and a combination of miR's might be even more effective. In the present study, miR-16 and miR-34a were transfected, singularly and in combination, in MPM cell lines H2052 and H28, and their effects on cell proliferation and sensitivity to cisplatin are reported. Interestingly, the overexpression of both miRs, alone or combined, slows down the cell cycle progression, modulates the p53 and HMGB1 expression and increases the sensitivity of cells to cisplatin, producing a marked impairment of cell proliferation and strengthening the apoptotic effect of the drug. However, the co-overexpression of the two miRs results more effective only in the regulation of the cell cycle, but does not enhance the sensitivity of MPM cells to cisplatin. Consequently, although the potential of miR-16 and miR-34a is confirmed, we must conclude that their combination does not improve the response of MPM to chemotherapy.

Antineoplastic drug occupational exposure: a new integrated approach to evaluate exposure and early genotoxic and cytotoxic effects by no-invasive Buccal Micronucleus Cytome Assay biomarker.

Health-care personnel handling antineoplastic drugs could be at risk for adverse health effects. We aimed to evaluate genotoxic and cytotoxic effects of antineoplastic drug exposure of personnel preparing and administering such drugs in three Oncology Hospitals in Italy enrolling 42 exposed subjects and 53 controls. Furthermore, we aimed to study the possible influence of XRCC1 and hOGG1 DNA repair genes polymorphisms on genotoxicity induced on buccal cells. We performed workplace and personal monitoring of some drugs and used exposure diary informations to characterize the exposure. Urinary 5-FU metabolite (α-fluoro-ß-alanine) was measured. Buccal Micronucleus Cytome (BMCyt) assay was used to evaluate DNA damage and other cellular anomalies. GEM and 5-FU contamination was found in 68% and 42% of wipe/swab samples respectively. GEM deposition was found on workers' pads while no α-fluoro-ß-alanine was found. BMCyt-assay showed higher genotoxicity and cytotoxicity on nurses administering antineoplastics than on preparators and controls. Among micronucleus (MN) positive (with MN frequency higher than 1.5‰) exposed subjects, the percentage of those carrying XRCC1 mut/het genotype was higher than in MN positive-controls. Using the sensitive BMCyt assay, we demonstrated that handling antineoplastics still represents a potential occupational health risk for workers that should be better trained/informed regarding such risks.

Human epithelial cells exposed to functionalized multiwalled carbon nanotubes: interactions and cell surface modifications.

With the expansion of the production and applications of multiwalled carbon nanotubes (MWCNTs) in several industrial and science branches, the potential adverse effects on human health have attracted attention. Numerous studies have been conducted to evaluate how chemical functionalization may affect MWCNT effects; however, controversial data have been reported, showing either increased or reduced toxicity. In particular, the impact of carboxylation on MWCNT cytotoxicity is far from being completely understood. The aim of this work was the evaluation of the modifications induced by carboxylated-MWCNTs (MWCNTs-COOH) on cell surface and the study of cell-MWCNT-COOH interactions by means of field emission scanning electron microscope (FESEM). Human pulmonary epithelial cells (A549) were incubated with MWCNTs-COOH for different exposure times and concentrations (10 µg/mL for 1, 2, 4 h; 5, 10, 20 µg/mL for 24 h). At short incubation time, MWCNTs-COOH were easily observed associated with plasma membrane and in contact with microvilli. After 24 h exposure, FESEM analysis revealed that MWCNTs-COOH induced evident changes in the cellular surface in comparison to control cells: treated cells showed blebs, holes and a depletion of the microvilli density in association with structure modifications, such as widening and/or lengthening. In particular, an increase of cells showing holes and microvilli structure alterations was observed at 20 µg/mL concentration. FESEM analysis showed nanotube agglomerates, of different sizes, entering into the cell with two different mechanisms: inward bending of the membrane followed by nanotube sinking, and nanotube internalization directly through holes. The observed morphological microvilli modifications, induced by MWCNTs-COOH, could affect epithelial functions, such as the control of surfactant production and secretion, leading to pathological conditions, such as alveolar proteinosis. More detailed studies will be, however, necessary to examine in depth the effects induced by MWCNTs-COOH and, in particular, the timing of the MWCNT-COOH-cell interaction.

A simple approach to measure the radon equilibrium factor F from air filter gross beta counting.

The internal alpha dose assessment (ICRP 65, 1994) depends on the value of the equilibrium factor F. This parameter is generally not measured and a mean conventional value ranging between 0.4 and 0.6 is assumed, possibly leading to a significant bias in the dose assessments. In this paper, a method for the measurement of F is reported, based on the total aerosol sampling on filters and immediate gross beta counting of 214Pb and 214Bi activities. Measurements are interpreted according to a Raabe-Wrenn and Jacobi simplified room model, leading to an estimate of the individual airborne activities of short-lived radon daughters, the removal parameter and the equilibrium factor. The method was laboratory tested and validated and it is being qualified by field surveys in different indoor environmental conditions.

Temporal variation of size-fractionated particulate matter and carbon monoxide in selected microenvironments of the Milan urban area.

This article focuses on air pollution in specific urban microenvironments and conditions characterized by high relative concentration levels and by possible risk to human health. For this reason, monitoring of particle number concentration (PNC) with a wide, size-resolved particle-size range, and CO (an indicator of combustion sources, e.g., traffic), was performed in a variety of microenvironments. Concentrations of ultrafine particles (UFPs), size-fractionated particulate matter (PM), and carbon monoxide (CO) were measured in the central area of Milan over three-week-long periods, one each during summer, autumn, and winter, with three monitoring sessions per day. Experimental data were collected continuously during each monitoring period along an established urban pathway. To assess the relevance of time and spatial factors affecting atmospheric concentrations of UFPs, PM, and CO data were collected while walking or moving by different private and public means of transport. Measurements were divided on the basis of different microenvironments (MEs), seasons, days of the week, and periods of the day. Data analysis shows statistically significant differences across MEs and monitoring periods. The highest measured median concentrations and data variability were observed for busy streets, walking or moving by motorized vehicle (CO, UFP) and in metro trains (PM); the lowest concentrations were observed in park areas and in indoor environments. The highest concentrations were measured during working day morning monitoring sessions. Regarding seasonal variation, UFP, PM, and CO showed different patterns: the highest median concentrations were observed in summer for CO, and in autumn and winter for the UFP and PM. Appreciable differences among all MEs and monitoring periods were observed: concentration patterns and variations appear related to typical sources of urban pollutants (traffic), proximity to sources, and time of day. [Supplementary materials are available for this article. Go to the publisher's online edition of Journal of Occupational and Environmental Hygiene for the following free supplemental resource: a file containing Table VI: Tau b (Kendall) index for non-parametric correlation tau test.].

[Environmental and biological monitoring in the plating industry]. / Monitoraggio ambientale e biologico nell'industria galvanica.

The work environment in the electroplating industry is characterized by a large amount of chemical substances used in the production process. The present work is a brief review of the time evolution of methods and strategies for the assessment of exposures to chromium and nickel by means of environmental and biological monitoring.

Airborne particulate matter and gaseous air pollutants in residential structures in Lodi province, Italy.

UNLABELLED: The province of Lodi is located in northern Italy on the Po River plain, where high background levels of air pollutants are prevalent. Lodi province is characterized by intensive agriculture, notably animal husbandry. This paper assesses indoor levels of selected airborne pollutants in 60 homes in the province, with special attention to size-fractionated particulate matter (PM). Indoor PM2.5 concentrations are frequently higher than current guidelines. PM10 and nitrogen dioxide also exceed the respective guideline recommendations in some cases, noting that 24-h nitrogen dioxide levels were compared with an annual limit value. All other studied pollutant levels are below current international guidelines. Among indoor PM size fractions, PM0.5 is predominant in terms of mass concentrations corresponding to 57% of PM10 in summer and 71% in winter. A strong seasonal trend is observed for all studied pollutants, with higher levels in winter corresponding to changes in ambient concentrations. The seasonal variation in PM10 is largely due to PM0.5 increase from summer to winter. Summer indoor PM levels are mainly from indoor-generated particles, while particles of outdoor origin represent the main contribution to winter indoor PM levels. On average, indoor concentrations of coarse PM are mostly constituted by indoor-generated particles. PRACTICAL IMPLICATIONS: This study presents a comparison between measured indoor concentrations in the study area and indoor air quality guideline criteria. Accordingly, particulate matter (PM) and NO2 are identified as key pollutants that may pose health concerns. It is also found that indoor PM in residential units is mainly constituted by particles with aerodynamic diameters <0.5 µm, especially in winter. Risk mitigation strategies should be focused on the reduction in indoor levels of NO2 and ultrafine and fine particles, both infiltrated from outdoors and generated by indoor sources.

[Improvement of a sedimentation method for measuring dispersion of fibres from asbestos cement roofs]. / Il metodo deposimetrico per la misura della dispersione di fibre di asbesto dalle coperture in cemento amianto: revisione e perfezionamento.

BACKGROUND: The present article is a follow-up of previous research, in which a sedimentation method was proposed to measure the dispersion of fibre bundles (primary pollution) from asbestos-cement roofs. OBJECTIVES: The aim of this study was to improve and standardize a screening method to evaluate asbestos bundle release from asbestos-containing materials. METHODS: An appropriate instrument (deposimetro) was used to passively sample asbestos on microscope slides by direct sedimentation. The microscopic analysis of samples was improved by the dispersion staining method, combined with the calculation of weight concentrations of asbestos per surface and time unit. The sampling efficiency was improved by introducing a new adhesive treatment of the microscope slides (85% stearyl alcohol, 15% octyldodecan) and a size cut-off restricting the counting method only to fibre bundles with diameters larger than 2 pm. RESULTS: The optimal sampling time was defined as 25-30 days without rain, extending the sampling time established in the previous investigation, and the optimal instrument position was defined at distances of 50 cm (vertical) and 0 cm (horizontal) from the roof edge. The effect of wind direction and velocity on asbestos release was also assessed, showing that wind gusts with a velocity of more than 10 m/s are mostly associated with dispersion peaks. CONCLUSIONS: A simple algorithm was proposed on the basis of field data (n=32) and 5 hazard classes were defined as a function of weight concentrations and asbestos type. The passive sampler is low in cost and is intended for use in large-scale surveys to identifY removal priorities.

[Monitoring latex risk: detection of airborne and glove allergens]. / Monitoraggio del rischio latice: campionamenti dell'allergene su particolato aerodisperso e su manufatti in gomma.

BACKGROUND: Latex is a relevant occupational and environmental allergen, strongly related to the extensive use of natural rubber products. OBJECTIVES: Threshold Limit Values have to be identified, as well as biocompatible materials in order to avoid sensitization or appearance of allergic symptoms. METHODS: In this paper we consider the main methods, which have been used to detecting latex allergens for environmental monitoring of airborne and latex products. RESULTS: We report our experience in such afield, and our approach to the latex problem, suggesting that quantification of allergens, which is currently applicable according to well standardized methods, should be adopted by manufacturers, agency and consumer organization.

Expression profile of ErbB receptor's family in human alveolar type 2-like cell line A549 exposed to hexavalent chromium.

Occupational exposure to hexavalent chromium (Cr (VI)) compounds is associated with increased risk of pulmonary disease. In the present study we have investigated temporal expression of ErbB's receptors family in A549 cells after exposure to Cr (VI). Treatment with 10 microM or 300 microM of Na2CrO4 induced apoptotic cell death within 24h. Based on data obtained by ELISA cell death detection method and fluorescence microscopy, the concentration of 10 microM was chosen to study the expression of ErbB receptors family. Such concentration reflects a condition of acute toxicity in which cells survived up to 24h. Real time quantitative PCR has been performed to analyze the expression profiles of ErbB family genes following chromium toxicity. The expression of EGFR and ErbB2 receptors was significantly reduced after 1h and 4h of treatment while ErbB2 receptor was significantly increased and EGFR receptor returned to basal value after 24h. Instead, ErbB3 receptor was overexpressed after 1h, returned to basal level after 4h and increased its level after 24h. Exposure to chromium did not change expression level of ErbB4 receptor in A549 cell line. The present data suggests that expression changes in ErbB receptors might have a role in the carcinogenic effects induced by this pneumotoxic agent.

Urinary hydroxylated metabolites of polycyclic aromatic hydrocarbons as biomarkers of exposure in asphalt workers.

BACKGROUND: Fumes and vapours released during laying of hot asphalt mix have been recognised as a major source of exposure for asphalt workers. OBJECTIVES: We investigated the relationships between inhalation exposure to asphalt emissions and urinary biomarkers of polycyclic aromatic hydrocarbons (PAHs) in asphalt workers (AW, n=75) and in ground construction workers (CW, n=37). METHODS: Total polyaromatic compounds (PAC) and 15 priority PAHs in inhaled air were measured by personal sampling. Hydroxylated PAH metabolites (OH-PAHs) (2-naphthol, 2-hydroxyfluorene, 3-hydroxyphenanthrene, 1-hydroxypyrene, 6-hydroxychrysene and 3-hydroxybenzo[a]pyrene) were determined in urine spot samples collected in three different times during the work week. RESULTS: Median vapour-phase PAC (5.5 microg m(-3)), PAHs (

[In vitro study of genotoxic and oxidative effects induced on human pulmonary cells by exposure to PAHs extracted from airborne particulate matter collected in a coke plant]. / Studio in vitro degli effetti genotossici ed ossidativi indotti su cellule polmonari umane dall'esposizione ad IPA estratti da matrici ambientali di una cokeria.

Genotoxic and oxidative effect of airborne particulate matter collected in a coke plant were evaluated on lung epithelial cells (A549). We aimed to clarify the mechanism of action of complex mixtures of PAHs and to identify biomarkers of effect of lung cancer. Particulate matter was analysed by GC/MS. Genotoxic and oxidative effects induced by the exposure to the extract were evaluated by Fpg comet assay. The cells were exposed for 30 min, 2h and 4h to 0.01%, 0.02% and 0.05% of the extract. We evaluated comet percentage and analysed tail moment values of exposed and unexposed cells treated with Fpg enzyme (TMenz) and untreated (TM) that indicate respectively oxidative and direct DNA damage. We found 0.328 ng/m3 of pyrene, 0.33 ng/m3 of benzo(a)anthracene, 1.073 ng/m3 of benzo(b)fluoranthene, 0.22 ng/m3 of benzo(k)fluoranthene, 0.35 ng/m3 of benzo(a)pyrene, 0.079 ng/m3 of dibenzo(a,h)anthracene and 0.40 ng/m3 of benzo(g,h,i)perylene. A dose-dependent increase, although not significant, of TM and TMenz in the exposed cells in respect to controls was found that indicates a slight increase of both direct and oxidative damage in exposed cells. A slight increase of comet percentage was found at the highest dose. We show the high sensibility of comet assay to measure early DNA damage also at low doses suggesting the use of such test on A549 to evaluate on target organ the effects of complex mixtures of genotoxic substances.

[Plastic industry and exposure to carcinogenic chemical agents: an Italian Multicentric Study in Lombardy]. / Stampaggio della plastica ed agenti chimici cancerogeni: l'esperienza dello studio PPTP-Plastica.

The potential carcinogenic risk at the workplaces is a primary interest of occupational health, but some questions are also controversially discussed. Particularly, in the plastic forming industry a great attention was directed to the hot processing and their possible exposure to monomers, some of which were classified as carcinogen by the International Agency for Research on Cancer (IARC) and/or the European Union (EU). In Lombardy, a study on occupational exposure to chemical carcinogens in the plastic forming industry was planned during last years. The aim was to recognize and promote preventive technical and medical solutions, basing on efficacy. By an investigation at workplace supported with standardized questionnaires, the presence of chemical carcinogens was registered in 59% of a representative sample of firms; but an effective possibility of exposure was found only for 34% of cases. The evaluation of exposure to monomers by air monitoring (acrylonitrile, 1,3-butadiene, styrene, formaldehyde), involving a representative sample of factory with ABS and formaldehydic resins processing, showed low level exposure, because the common hygienic prevention measures were applied; some particular occupation shoved greater exposure to formaldehyde.

Sister chromatid exchange and oxidative DNA damage in paving workers exposed to PAHs.

Paving workers are exposed during road paving to several polycyclic aromatic hydrocarbons (PAHs) contained in asphalt fumes. In this study early genotoxic and oxidative effects of exposure to bitumen fumes were evaluated in 19 paving workers and 22 controls. Environmental and biological monitoring of exposure was carried out, measuring, on personal air samples from exposed workers collected during three working days, the concentration of 14 PAHs and urinary OH-pyrene at the end of each of the three working days. Genotoxic effect was evaluated analysing sister chromatid exchange (SCE) frequency and direct-oxidative DNA damage by formamido-pyrimidine-glycosylase (Fpg)-modified comet assay on lymphocytes. Tail moment values from Fpg-enzyme treated cells (TMenz) and from untreated cells (TM) were used as parameters of direct and oxidative DNA damage, respectively. For each subject, the TMenz/TM ratio >2.0 was used to indicate the presence of oxidative damage. DNA damage was also evaluated analysing comet percentage. Personal air samples showed low level of total PAHs (2.843 microg m(-3)) with prevalence of 2-3 ring PAHs (2.693 microg m(-3)). Urinary OH-pyrene after work-shift of the three working days was significantly higher than that found at the beginning of the working week. SCE analysis did not show any difference between two groups while an oxidative DNA damage was found in 37% of exposed with respect to the absence in controls. Comet percentage was significantly higher (P = 0.000 ANOVA) in the exposed than in controls. The results demonstrate the high sensitivity of comet assay to assess early oxidative effects induced by exposure to bitumen fumes at low doses and confirm the suitability of urinary OH-pyrene as a biomarker of PAH exposure. In conclusion the study suggests the use of Fpg-modified comet test as a biomarker of early genotoxic effects and that of urinary OH-pyrene as a biomarker of PAH exposure to furnish indications in terms of characterization, prevention and management of risk in occupational exposure to mixtures of potentially carcinogenic substances.

[Study of genotoxic and oxidative effects induced by PAH exposure in paving workers]. / Studio degli effetti genotossici ed ossidativi indotti dall'esposizione ad IPA in lavoratori addetti alla pavimentazione stradale.

Paving workers are exposed during road paving to several PAHs contained in asphalt fumes. We aimed to evaluate early genotoxic and oxidative effects in 19 paving workers and 22 controls. We analysed sister chromatide exchange (SCE) frequency as marker of genotoxicity. Moreover we assessed oxidative DNA damage by Fpg-modified comet assay on lymphocytes calculating tail moment values from fpg-enzyme treated cells (TMenz) and from untreated cells (TM). For each subject the TMenz/TM ratio higher than 2.0 was used to indicate the presence of oxidative damage. We also evaluated DNA damage analysing comet percentage. SCE analysis didn't show any difference between exposed and control groups. We found oxidative DNA damage in 37% of exposed in respect to the absence in controls. Comet percentage was significantly higher in the exposed than in controls. The results demonstrate the high sensitivity of comet assay to assess early oxidative effects induced by exposure to PAH mixtures at low doses and suggest the use of this biomarker in the characterization, prevention and management of risk induced by occupational exposure to mixtures of potentially carcinogenic substances.

[Assessment of exposure to organic aromatic compounds and PAH in asphalt industry: the PPTP-POPA Study results]. / Valutazione dell'esposizione a composti organici aromatici e IPA nelle opere di asfaltatura: i risultati dello Studio PPTP-POPA.

Asphalt is a mixture of mineral matter and bitumen, its fumes contain about 1% of Polycyclic Aromatic Hydrocarbons (PAH), some of which are carcinogens. In the PPTP-POPA Study of Lombardy Region, a group of 100 asphalt workers (exposed to bitumen fumes and diesel exhausts) and a group of 47 ground construction operators (exposed only to diesel exhausts) were investigated to assess PAH exposure in Italy, by means of environmental-air monitoring (the 16 most relevant, according to the American Environmental Protection Agency, EPA) and biological monitoring (urinary 1-hydroxypyrene excretion). Our results show that PAH exposure in these workers is not higher than that observed in traffic policemen working in urban areas. Since dermal exposure has been suggested as a major determinant of the total PAH dose absorbed by road pavers from bitumen fumes, we assessed skin contamination by organic aromatic compounds and by sixteen PAH: in both groups, six pads were applied to each subject in different parts of the body, during the workshift. The results show that the dermal contamination in road pavers is higher than in ground construction operators and that cutaneous dose rate is higher than respiratory dose rate, whereas the amount of absorption the ratio is inverted.

[Indoor air quality: suggestions for risk assessment and medical surveillance]. / Qualità dell'aria degli ambienti confinati non industriali: indicazioni per la valutazione del rischio e la sorveglianza sanitaria.

This paper presents indications for investigations and health surveillance in indoor environments. The study of the indoor air quality consists of the following phases: acquisition of the necessary information about the indoor environment; sampling strategy and techniques; qualitative and quantitative analysis of contaminants such as particulate, CO2 and CO, NOx, volatile organic compounds, biological agents. The proposed health surveillance is articulated on four lines: periodical health surveillance, when already performed for other risks (e.g. VDT); specific clinical examinations in occasion of particular events; use of a questionnaire for the evaluation of comfort of the workers; health promotion. A team approach, with cooperation between technical and medical experts, is recommended both for periodical risk assessment and when it is necessary to solve specific indoor problems.

Evaluation of oxidative damage and inhibition of DNA repair in an in vitro study of nickel exposure.

It has been suggested that Nickel is involved in oxidative damage and inhibition of DNA repair. We studied the effects of NiSO4 on oxidative stress and DNA repair in Jurkat cells to elucidate its mechanism of action. Cells were treated with H2O2 and ROS generation (by flow cytometry), and oxidative DNA damage (as tail moment by Fpg-enzyme comet test), were evaluated immediately and after 4 and 24 h of DNA damage recovery occurred in presence or absence of NiSO4 (0.017 and 0.17 microM) to clarify possible interactions of Ni with DNA repair processes. Moreover, cells were exposed to the same doses of NiSO4 for 4 and 24 hours to evaluate its direct oxidative effect. The results of the comet test showed high tail moment immediately after oxidative burst with a decreasing after 4 h of DNA recovery, and a slight increase after 24 h of recovery. The decreases were more limited for cells treated with NiSO4 0.17 microM indicating an inhibition of oxidative DNA damage repair by this substance. An induction of ROS was observed after 4 h of incubation with higher dose of NiSO4. Cells treated with H2O2 showed the highest level of ROS after 4 h of recovery in presence of NiSO4 0.17 microM that remained at elevated levels also after 24 h of recovery suggesting a synergistic action of Ni with H2O2 in the reduction of cellular anti-oxidative defence activities.