Health effects of living near an incinerator: A systematic review of epidemiological studies, with focus on last generation plants.

Huge reductions in incinerators' emissions occurred over time, and results of older studies cannot be directly generalized to modern plants. We conducted a systematic review of the epidemiologic evidence of the health effects of incinerators, classifying plants in three generations, according to emission limits. A systematic search identified 63 epidemiologic studies, published in English, investigating health effects of incinerators on humans. We focused on cancer, cardio-cerebrovascular diseases (CVD) and respiratory diseases, pregnancy outcomes and congenital anomalies. Only six studies in the general population were on third generation incinerators providing data on pregnancy outcomes and congenital anomalies. Given the heterogeneity of methods, the abundance of ecological/semi-ecological studies and the lack of reliable quantitative measures of exposure in several studies we did not perform any meta-analysis. No excesses emerged concerning all cancers and lung cancer. An excess of non-Hodgkin lymphoma was reported in some earlier studies, but not for second generation plants. Possible excesses of soft tissue sarcomas were confined to earlier incinerators and the areas closer to the plants. No clear association emerged for CVD and diseases of the respiratory system. Several different pregnancy outcomes were considered, and no consistent association emerged, in spite of a few positive results. Studies were negative for congenital anomalies as a whole. Sporadic excesses were reported in a few studies for specific types of anomalies, but no consistent pattern emerged. Evaluation of the evidence was hindered by heterogeneity in reporting and classification of outcomes across studies. Direct evidence from third generation plants is scarce. Methodological issues in study design (mainly related to exposure assessment, confounding and ecological design) and analysis make interpretation of results complex. In spite of this, the overall evidence suggests that, if there were any excesses at all for older incinerators, they were modest at most. Additional monitoring of third generation plants needs to overcome methodological weaknesses.

Occupational exposure to formaldehyde and risk of non hodgkin lymphoma: a meta-analysis.

BACKGROUND: Formaldehyde, a widely used chemical, is considered a human carcinogen. We report the results of a meta-analyses of studies on the relationship between occupational exposure to formaldehyde and risk of non-Hodgkin lymphoma (NHL). METHODS: We performed a systematic review and meta-analysis according to international guidelines and we identified 12 reports of occupational populations exposed to formaldehyde. We evaluated inter-study heterogeneity and we applied a random effects model. We conducted a cumulative meta-analysis and a meta-analysis according to estimated average exposure of each study population. RESULTS: The meta-analysis resulted in a summary relative risk (RR) for NHL of 0.93 (95% confidence interval 0.83-1.04). The cumulative meta-analysis suggests that higher RRs were detected in studies published before 1986, while studies available after 1986 did not show an association. No differences were found between different levels of occupational exposure. Conclusions Notwithstanding some limitations, the results of this meta-analysis do not support the hypothesis of an association between occupational exposure to formaldehyde and risk of NHL.

Position Paper on Asbestos of the Italian Society of Occupational Medicine.

The Position Paper (PP) on asbestos of the Italian Society of Occupational Medicine (SIML) aims at providing a tool to the occupational physician to address current diagnostic criteria and results of epidemiological studies, and their consequences in terms of preventive and evaluation actions for insurance, compensation and litigation. The PP was based on an extensive review of the scientific literature and was compiled by a Working Group comprising researchers who have contributed to the international literature on asbestos-related diseases, as well as occupational physicians with extensive experience in the evaluation of risks and the medical surveillance of workers currently and formerly exposed to asbestos. The PP was drafted and reviewed between 2017 and 2018; its final version was prepared according to the guidelines of AGREE Reporting Checklist. All the members of the Working Group subscribed to the document, which was eventually approved by SIML's Executive Committee. The first section addresses industrial hygiene issues, such as methods for environmental monitoring, advantages and limitations of different microscopy techniques, the potential role of microfibers and approaches for retrospective assessment of exposure, in particular in epidemiological studies. The second section reviews the biological effects of asbestos with particular attention to the diagnostic aspects of asbestosis, pleural changes, mesothelioma and lung cancer. In the following section the criteria of causal attribution are discussed, together with different hypotheses on the form of the risk functions, with a comparison of the opinions prevalent in the literature. In particular, the models of the risk function for mesothelioma were examined, in the light of the hypothesis of an acceleration or anticipation of the events in relation to the dose. The last section discusses topics of immediate relevance for the occupational physician, such as health surveillance of former exposed and of workers currently exposed in remediation activities.

Biological monitoring of exposure to low concentrations of benzene in workers at a metallurgical coke production plant: new insights into S-phenylmercapturic acid and urinary benzene.

CONTEXT: Urinary S-phenylmercapturic acid (SPMA) and benzene (U-Ben) are usually measured at the end of the work shift (ES), although their kinetic of elimination is not clearly known. OBJECTIVE: To investigate SPMA and U-Ben elimination 16 h after the ES, in 93 coke production workers exposed to low benzene concentrations. MATERIALS AND METHODS: Airborne benzene (A-Ben) was measured by passive samplings, while SPMA, U-Ben, methyl-tert-butyl ether (U-MTBE), cotinine (U-Cot) and creatinine were determined on urine samples collected at ES and before the beginning of the next work shift (next BS). RESULTS: Median A-Ben concentrations were 17.2 µg/m3 in the personal and 34.7 µg/m3 in the stationary samplings. SPMA was always detectable, whereas U-Ben was below the limit of quantification in 26.7% of the ES and 35.6% of the next BS samples, and U-MTBE in more than the 80.0% of the samples. At both the sampling times, SPMA and U-Ben showed a positive dependence on personal A-Ben, as well as on creatinine and U-Cot values. DISCUSSION AND CONCLUSION: SPMA and U-Ben at the next BS were dependent on the exposure to low benzene concentrations suffered in the previous work shift, prompting a reconsideration of the urine sampling time recommended by the American Conference Governmental Industrial Hygienists (ACGIH).

The Repair of Skeletal Muscle Requires Iron Recycling through Macrophage Ferroportin.

Macrophages recruited at the site of sterile muscle damage play an essential role in the regeneration of the tissue. In this article, we report that the selective disruption of macrophage ferroportin (Fpn) results in iron accumulation within muscle-infiltrating macrophages and jeopardizes muscle healing, prompting fat accumulation. Macrophages isolated from the tissue at early time points after injury express ferritin H, CD163, and hemeoxygenase-1, indicating that they can uptake heme and store iron. At later time points they upregulate Fpn expression, thus acquiring the ability to release the metal. Transferrin-mediated iron uptake by regenerating myofibers occurs independently of systemic iron homeostasis. The inhibition of macrophage iron export via the silencing of Fpn results in regenerating muscles with smaller myofibers and fat accumulation. These results highlight the existence of a local pathway of iron recycling that plays a nonredundant role in the myogenic differentiation of muscle precursors, limiting the adipose degeneration of the tissue.

Biological monitoring of exposure to polycyclic aromatic hydrocarbons and to metallic elements in Italian Navy workers operating near the industrial area in Taranto (South Italy).

OBJECTIVES: To assess, by means of biological monitoring, exposure to polycyclic aromatic hydrocarbons (PAHs) and to metallic elements in Italian Navy workers operating near the industrial area in Taranto, and thereby estimate the health risk. METHODS: A total of 450 workers in the Italian Navy were examined; they had office type jobs, and 150 of them worked near the industrial area in Taranto (exposed group), 150 in Taranto but far from this area (internal control group) and 150 in Brindisi (external control group). The recruited workers were administered a questionnaire inquiring about current and previous working activities, personal medical history, lifestyle and dietary habits, and their residence location. Then they collected a urine sample for the determination of 1-hydroxypyrene, 2-naphthol, cotinine and the metallic elements As, Cd, Co, Cr, Mn, Ni, Pb, Cu, Zn and Hg. The latter were measured in 110 workers in each group. In addition, in some of the work sites of the three groups, environmental samplings were carried out to determine PAHs and the 10 metallic elements, also taking into account the wind direction. RESULTS: Airborne benzo(a)pyrene concentrations at the different sampling sites ranged from 0.02 to 0.06 ng/m3 and naphthalene between <25 and 65.3 ng/m3, regardless of the wind direction. Among the metallic elements, As, Cd, Co, Cr, Hg, Pb, Cu and Zn were present at concentrations below or just above the limit of detection (LOD). Mn and Ni were slightly higher in the work sites of the exposed group. The urinary concentrations of 1-hydroxypyrene, 2-naphthol and the single metallic elements were not higher in the exposed workers group than in the other 2 groups. Smokers had significantly higher urinary 1-hydroxypyrene and 2-naphthol concentrations, whereas cigarette smoking did not condition a higher urinary elimination of metallic elements in the three groups with the exception of Cd and Pb. Moreover, residence location conditioned Mn, Hg and As urinary excretion, consumption of shellfish and/or crustaceans in the 72 hours before urine collection conditioned As elimination, and consumption of legumes in the 72 hours before urine collection conditioned Ni elimination. CONCLUSIONS: This research did not find a higher urinary excretion of 1-hydroxypyrene, 2-naphthol and As, Cd, Co, Cr, Mn, Ni, Pb, Cu, Zn and Hg in the exposed workers group as compared to the internal control group working far from the industrial area of Taranto, nor in the group working in another city far away from Taranto, Brindisi. Therefore, it indicated that workers in the Italian Navy operating near the industrial area in Taranto were not exposed to a greater risk attributable to exposure to PAHs and metallic elements than the two control groups.

Effects of metal-rich particulate matter exposure on exogenous and endogenous viral sequence methylation in healthy steel-workers.

BACKGROUND: Inhaled particles have been shown to produce systemic changes in DNA methylation. Global hypomethylation has been associated to viral sequence reactivation, possibly linked to the activation of pro-inflammatory pathways occurring after exposure. This observation provides a rationale to investigate viral sequence (both exogenous and endogenous) methylation in association to metal-rich particulate matter exposure. To verify this hypothesis, we chose the Wp promoter of the Epstein-Barr Virus (EBV-Wp) and the promoter of the human-endogenous-retrovirus w (HERV-w), respectively as a paradigm of an exogenous and an endogenous retroviral sequence, to be investigated by bisulfite PCR Pyrosequencing. We enrolled 63 male workers in an electric furnace steel plant, exposed to high level of metal-rich particulate matter. RESULTS: Comparing samples obtained in the first day of a work week (time 0-baseline, after 2 days off work) and the samples obtained after 3 days of work (time 1-post exposure), the mean methylation of EBV-Wp was significantly higher at baseline compared to post-exposure (meanbaseline = 56.7%5mC; meanpost-exposure = 47.9%5mC; p-value = 0.009), whereas the mean methylation of HERV-w did not significantly differ. Individual exposure to inhalable particles and metals was estimated based on measures in all working areas and time spent by the study subjects in each area. In a regression model adjusted for age, body mass index and smoking, PM and metal components had a positive association with EBV-Wp methylation (i.e. PM10: ß = 5.99, p-value < 0.038; nickel: ß = 17.82, p-value = 0.02; arsenic: ß = 13.59, p-value < 0.015). CONCLUSIONS: The difference observed comparing baseline and post-exposure samples may be suggestive of a rapid change in EBV methylation induced by air particles, while correlation between EBV methylation and PM/metal exposure may represent a more stable adaptive mechanism. Future studies investigating a larger panel of viral sequences could better elucidate possible mechanisms and their role in pro-inflammatory pathways leading to systemic health effects.

Birth and development of the SIMLII Guidelines program.

OBJECTIVES: This paper aims to review the steps that the Italian Society Occupational Medicine and Industrial Hygiene (SIMLII) has undertaken over the past two decades in the context of a process of integration with quality systems, resulting in several initiatives including the production of different tools for the updating and professional qualification of the Occupational Health Physician (OHP). METHODS: The choice of focusing on a propositional-formative model such as the guidelines (GL) and the choice of the topics to be dealt with, was based on the need to provide the OHP with appropriate tools in order to face the complexity, specificity and rapidity of knowledge evolution which characterize our discipline. RESULTS: After the release of the first set of instruments (25 GL) over the five-year period 2003-2008, it became necessary to adhere to the guidelines of the GL National Program, distinguishing GL's evidence based, from consensus / orientation documents or technical assessments. CONCLUSIONS: In recent years, the introduction of the AGREE method has been of great interest and importance for assessing the quality of content and recommendations, also considering the recent legislation provisions on the criminal and civil liability of the Physician.

[Reference values: from guidance values to the exposome.] / Valori di riferimento: dai valori guida all'esposoma.

OBJECTIVES: The correspondence between biomarkers and the complex interaction of toxics with the human organism has been fully described years ago by the American National Research Council which developed a precious diagram. METHODS: This model is still valid in describing the new methodologic agnostic or "omic" approaches to the science of exposure. RESULTS: Reference values and exposome share indeed the search for internal dose biomarkers; adduttomics may be seen as an evolution of the target dose markers while epigenetics itself is a new way of exploring the world of early effect biomarkers.

[Exposome: from an intuition to a mandatory research field in occupational and enviromental medicine.] / Esposoma: da intuizione a linea di ricerca obbligata nelle Scienze Mediche Occupazionali e Ambientali.

OBJECTIVES: As Genomics aims at the collective characterization and quantification of genes, exposomics refers to the totality of lifetime environmental exposures, consisting in a novel approach to studying the role of the environment in human disease. The aim is to assess all human environmental and occupational exposures in order to better understand their contribution to human diseases. The "omics" revolution infact mostly regards the underlying method: scientific knowledge is expected to come from the analysis of increasingly extensive databases. METHODS: The primary focus is on air pollution and water contaminants, but all the determinants of human exposure are conceptually part of the idea of exposome, including physical and psychological factors. Using 'omic' techniques the collected exposure data can be linked to biochemical and molecular changes in our body. RESULTS: Since the first formulation of the idea itself of Exposome many efforts have been made to translate the concept into research, in particular two important studies have been started in Europe. CONCLUSIONS: We herein suggest that Occupational Medicine could be a precious contributor to the growth of exposure science also in its omic side thanks to the methods and to the knowledges part of our background.

Occupational Medicine in Italian Academy: what future? / Dare un future alla Medicina del Lavoro nelle Università itaiane?

The entire Italian University system, including the whole field of medical teaching and research, is currently passing through a period of cumbersome changes due to the many difficulties encountered in its reform process. Academic occupational medicine is deeply involved in this process that resembles a real crisis. Given this background, this contribution - written as President of the Italian College of Occupational Medicine Full Professors - has the main objective to open a debate about the current generalized crisis of our Academic Discipline and about its possible future developments. Questions that appear most relevant to the nearly forty University Institutes we are working in include: The constantly decreasing number of professors and researchers (presently about 20 full professors, 50 associate professors and 60 researchers); the reduced ability to recruit young researchers; the contraction of resources and funds; the difficult coordination with other clinical and prevention disciplines in teaching activities. Despite this, points of scientific and professional excellence in many fields exist in our Institutes: from toxicology and epidemiology, to respiratory diseases and ergonomics, to evidence based prevention and quality systems promotion. The expected debate should facilitate new organizational links within and across Universities in order to gain critical masses, improve capabilities in new fields of research (as dose and effect indicators and their matrices, epigenetics, exposomics, connection of exposure data with epidemiological  evidences), innovate and expand teaching (in Medical Schools courses and in Residency programs), and advance clinical-diagnostic practices in University Hospitals.

Assessment of residual exposure to PCBs in metallurgy.

OBJECTIVE: To evaluate the occupational exposure to polychlorinated biphenyls (PCBs) in 56 workers employed in 6 electric arc furnace steelmaking plants and 2 secondary aluminum smelting plants located in the highly industrialized area of Brescia, Northern Italy. METHODS: Thirty-four PCB congeners were found in both environmental and biological samples from workers engaged in scrap yards, electric arc furnaces, casting and maintenance departments. RESULTS: The highest airborne PCB levels were found in the aluminum plant, even 100 times those detected in the steelwork plants. Dioxin-like PCB congeners (DL-PCBs) were poorly represented in all biological samples, whereas non Dioxin-Like PCB congeners (noDL-PCBs), in particular environmentally widespread congeners (PCB 153, 138, 180), could be detected in almost all samples. The mean total PCB serum level was 3.9 ng/ml, with a range of 1.3-10.3 ng/ml, while the geometric mean for airborne PCBs levels was 9305 pg/m3, with a range of 1138-217806 pg/m3. CONCLUSIONS: Despite the higher PCB values recorded in some metallurgical plant workplaces, we failed to find any significant difference between serum concentrations in workers from steel or aluminum production, even in consideration of different tasks or different job seniority, while positive association was found only according to the age of the workers. A possible explanation may be identified in the effectiveness of the individual and collective preventive measures adopted in the workplace. Assessment of the occupational exposure to such compounds, in consideration of the recent classifications as carcinogenic to humans, should be encouraged.

Methodology to define biological reference values in the environmental and occupational fields: the contribution of the Italian Society for Reference Values (SIVR).

BACKGROUND: Biological reference values (RVs) explore the relationships between humans and their environment and habits. RVs are fundamental in the environmental field for assessing illnesses possibly associated with environmental pollution, and also in the occupational field, especially in the absence of established biological or environmental limits. OBJECTIVES: The Italian Society for Reference Values (SIVR) determined to test criteria and procedures for the definition of RVs to be used in the environmental and occupational fields. METHODS: The paper describes the SIVR methodology for defining RVs of xenobiotics and their metabolites. Aspects regarding the choice of population sample, the quality of analytical data, statistical analysis and control of variability factors are considered. The simultaneous interlaboratory circuits involved can be expected to increasingly improve the quality of the analytical data. RESULTS: Examples of RVs produced by SIVR are presented. In particular, levels of chromium, mercury, ethylenethiourea, 3,5,6-trichloro-2-pyridinol, 2,5-hexanedione, 1-hydroxypyrene and t,t-muconic acid measured in urine and expressed in micrograms/g creatinine (µg/g creat) or micrograms/L (µg/L) are reported. CONCLUSIONS: With the proposed procedure, SIVR intends to make its activities known to the scientific community in order to increase the number of laboratories involved in the definition of RVs for the Italian population. More research is needed to obtain further RVs in different biological matrices, such as hair, nails and exhaled breath. It is also necessary to update and improve the present reference values and broaden the portfolio of chemicals for which RVs are available. In the near future, SIVR intends to expand its scientific activity by using a multivariate approach for xenobiotics that may have a common origin, and to define RVs separately for children who may be exposed more than adults and be more vulnerable.

Microvesicle-associated microRNA expression is altered upon particulate matter exposure in healthy workers and in A549 cells.

Cardiovascular disease risk has been consistently linked with particulate matter (PM) exposure. Cell-derived microvesicles (MVs) are released into plasma and transfer microRNAs (miRNAs) between tissues. MVs can be produced by the respiratory system in response to proinflammatory triggers, enter the circulatory system and remotely modify gene expression in cardiovascular tissues. However, whether PM affects MV signaling has never been investigated. In this study, we evaluated expression of microRNAs contained within plasma MVs upon PM exposure both in vivo and in vitro. In the in vivo study, we isolated plasma MVs from healthy steel plant workers before and after workplace PM exposure. We measured the expression of 88 MV-associated miRNAs by real-time polymerase chain reaction. To assess a possible source of the MV miRNAs identified in vivo, we measured their miRNA expression in PM-treated A549 pulmonary cell lines in vitro. MiRNA profiling of plasma MVs showed 5.62- and 13.95-fold increased expression of miR-128 and miR-302c, respectively, after 3 days of workplace PM exposure (P < 0.001). According to Ingenuity Pathway Analysis, miR-128 is part of coronary artery disease pathways, and miR-302c is part of coronary artery disease, cardiac hypertrophy and heart failure pathways. In vitro experiments confirmed a dose-dependent expression of miR-128 in MVs released from A549 cells after 6 h of PM treatment (P = 0.030). MiR-302c was expressed neither from A549 cells nor in reference lung RNA. These results suggest novel PM-activated molecular mechanisms that may mediate the effects of air pollution and could lead to the identification of new diagnostic and therapeutic interventions.

[The teaching of occupational medicine in the Master of Science in Medicine in the twenty years since the introduction of Table XVIII]. / L'insegnamento della Medicina del lavoro nel corso di laurea magistrale in Medicina e Chirurgia a vent'anni dall'introduzione della Tabella XVIII.

In 1991, the implementation of the new programme for education and training in Medicine and Surgery has introduced the teaching of Occupational Medicine (OM) as a compulsory subject for all medical students. After two decades from that event and in conjunction with the implementation of the new academic departments introduced by the law 240/2010, the aim of the present study was to address the current status and the main characteristics of education and training, including clinical activities, in OM in Italian Universities and to update the information on the related academic human resources available. A questionnaire was developed to investigate the different features of the academic staff belonging to the area of OM (SSD MED/44), and to evaluate the organization of teaching and the clinical activities performed by the Occupational Medicine sections. The results showed that among the 40 Italian universities with a degree course in Medicine and Surgery, 67% of them have at least one full professor, 72% one associate professor and 78% one assistant professor belonging to the area of OM. Nevertheless, a steady decrease in the number of academic staff is observed with time, which caused a lack of presence of the discipline in some universities. In most degree courses in Medicine and Surgery the teaching of OM is usually included in an integrated course together with other disciplines such as General and Applied Hygiene and/or Forensic and Legal Medicine. Within the integrated course the number of University Education & Training Credits (CFU, corresponding to approx. 25 hrs of teaching overall) assigned to OM is generally between 2 and 3 (61% of cases). The teaching of OM is also present in eight different master degree courses (MSc) and in 33 different triennial degree courses (BSc). To support the teaching clinical activities, such as workers' health surveillance, laboratories, ambulatories, and DH or inpatient activities are performed, in one or more of these forms, by almost all of the OM institutions. The findings of this study, despite being subject to change rapidly with time, still provide an invaluable set of information and should represent, therefore, a rational basis for planning the future recruitment of academic staff and for updating the contents and methodologies of graduate education and training in Occupational Medicine in Italian universities.

[Considerations on the use of meta-analyses in the orientation of knowledge and decisions in Occupational Medicine]. / Riflessioni sull'impiego della meta-analisi nell'orientamento delle conoscenze e delle decisioni in Medicina (del Lavoro).

In recent years, due to the need to elaborate the amount of information available from the scientific literature, the meta-analyses and systematic reviews have become very numerous. The meta-analyses are carried out to evaluate the association between two events when single researches haven't provided comprehensive data. On the other hand, a good meta-analysis must satisfy certain criteria, from the selection of the studies until the evaluation of the outcomes; to this purpose, the application of methods for quality assessment is a crucial point to obtain data of adequate reliability. The aim of this review is to give some introductory tools for a critical approach to meta-analyses and systematic reviews, which have become useful instruments also in occupational medicine.

Metal-on-metal hip prostheses: correlation between debris in the synovial fluid and levels of cobalt and chromium ions in the bloodstream.

PURPOSE: Hip prostheses with metal-on-metal (MoM) coupling can release cobalt-chromium particles and ions. The aim of this work is to verify the correlation between particles in the synovial fluid and circulating ions. METHODS: Forty patients were enrolled; particles from synovial fluid were analysed by SEM­EDX (Scanning Electron Microscopy-Energy Dispersion X-rays analysis) and levels of circulating Co and Cr were assayed by ICP-MS (inductively-coupled plasma mass spectrometry). RESULTS: In 16 cases we did not find any particles in the synovial fluid and the Co level in whole blood was 0.05­4.42 ppb; in seven with few particles the blood level was 2.2­15.6 ppb; in six cases with several particles the level was 5.0­54.3 ppb; finally, in 11 cases we isolated not only Co-Cr particles, but also Cr particles with low or absent Co and in these patients the circulating level of Co was 23.8­109.6 ppb. Co in serumand Cr level both whole blood and serum have shown a similar trend to Co; the correlation between all these values and the corresponding particles is statistically significant in all cases. CONCLUSION: Co and Cr both in serum and whole blood represents a systemic representation of the particle release at local level and can therefore be used to confirm a diagnosis and monitor the wear process of MoM articular prostheses.

[Quality assurance systems and occupational medicine system: an history twenty years along]. / Qualità e Medicina del Lavoro, 20 anni dopo.

Along the last tventy years, in our country the quality assurance systems and the occupational medicine deeply interacted both in theoretical and practical fields of interest at three levels: (i) the need of preventive and therefore of occupational medicine in quality assurance systems; (ii) the need on reverse of quality in prevention and occupational mnedicine mainly in qualification and updating process; (iii) the evidence, proofs of efficacy or appropriateness of different preventive procedures and occupational physician activities; (iv) the connection with European and national legal directives and with technical or good practice norms. Finally we discuss about the role of occupational physician as the global consultant for enterprise, as a mandatory strategic technical figure in a typical multidisciplinary processes as the implementation of the quality systems.