A novel approach for geographical risk mapping of morbidity and mortality rates: the case of Val D'Agri, Italy.

While associations between exposure to air pollutants and increased morbidity and mortality are well established, few rigorous studies on this issue are available. The aim of the current study is to implement a new approach to the spatial analysis of mortality and morbidity, based on testing for the presence of the same association in other areas of similar size. Additionally, we perform a case study in Val d'Agri (VA), an area of Basilicata Region, Southern Italy, where oil and natural gas extraction began in 1998. In order to examine the spatial distribution of morbidity and mortality in the region of interest, Hospital discharge (2001-2013) and mortality (2003-2014) rates for the main environment-related diseases were calculated. In addition, a comparison between the period 1980-1998 and the period 1999-2014 was performed for cardiovascular disease mortality. For the period under study, a neutral scenario emerged for cancer and respiratory diseases, where we found no differences in morbidity and mortality as compared to the national benchmark. In some cases significantly lower values (as compared to the nation-wide benchmark) were found. Conversely, a slight excess in morbidity and mortality (as compared to the nation-wide benchmark) emerged for cardiovascular diseases. Still, this excess was common to a number of municipalities in the surroundings of VA, and appeared to be already present in 1980. Higher rates of cardiovascular diseases, lower rates of neoplastic disorders no differences in mortality for respiratory causes (as compared to the nation-wide benchmark) were found in multiple areas of the region, and were therefore not specific to VA. In summary, our data do not support the hypothesis of a role of industrial activities related to oil extraction in VA in determining mortality and morbidity patterns and trends.

[Population health surveillance of the general population living near Turin (Northern Italy) incinerator (SPoTT): methodology of the study]. / Sorveglianza sulla salute della popolazione nei pressi del termovalorizzatore di Torino (SPoTT): presentazione del programma di sorveglianza.

Si intende qui descrivere il sistema di sorveglianza sugli effetti sulla salute (SpoTT) dell'inquinamento ambientale nelle aree circostanti l'inceneritore di Torino. SPoTT ha 3 linee di attività: 1. monitoraggio epidemiologico degli effetti a breve termine attraverso analisi temporali e misura della correlazione tra livelli giornalieri di emissioni dell'impianto e andamento degli eventi individuati dagli archivi dei dimessi (SDO), di pronto soccorso e di mortalità; sono coinvolti coloro che nel 2013-2018 risiedevano nell'area di ricaduta delle emissioni; 2. sorveglianza epidemiologica degli effetti a lungo termine, stimando tassi standardizzati di mortalità e morbosità; a ogni soggetto è attribuito il valore stimato di esposizione cumulato nel tempo caratteristico della residenza anagrafica; le informazioni sulla salute sono reperite dagli archivi SDO, di mortalità e dai certificati di assistenza al parto; sono studiati due decenni pre-post l'avvio dell'impianto: 2003-2012 e 2013-2022; 3. monitoraggio biologico con misurazione pre-post di metalli, PCDD/F, PCB, OH-IPA; sono coinvolti 196 residenti esposti e 196 di controllo di 35-69 anni, campionati a caso dalle anagrafi comunali; sono effettuate misure di funzionalità endocrina e respiratoria, pressione arteriosa, rischio cardiovascolare; l'esposizione cumulativa sarà stimata per ciascuna persona campionata integrando l'indirizzo di residenza, il tempo di permanenza in ciascun indirizzo e i dati ricavati dai modelli di ricaduta; sarà costituita una biobanca per future indagini di laboratorio; sono coinvolti anche 20 allevatori e i lavoratori dell'impianto. Una quarta linea di attività, non descritta in questo articolo, riguarda il monitoraggio della salute dei lavoratori addetti all'impianto. SPoTT è il primo studio in Italia su inceneritori e salute che adotta un disegno di studio longitudinale di adeguata potenza sia per i residenti sia per i lavoratori. I primi risultati sono attesi nel corso del 2016.

Human biomonitoring of metals in adults living near a waste-to-energy incinerator in ante-operam phase: Focus on reference values and health-based assessments.

The human biomonitoring (HBM) of metals is a part of the ongoing project SPoTT for the longitudinal health surveillance of the population living near a waste-to-energy (WTE) incinerator (Turin, Italy). The HBM of metals in the SPoTT population aimed to evaluate: i) reference values (RVs) before the WTE incinerator started operation; ii) differences in exposure by variables; iii) variations respect to other HBM studies; iv) exposure that exceeds the available health-based benchmarks as the Biomonitoring Equivalents (BEs) for urine Cd and Human Biomonitoring (HBM-I and HBM-II) values for urine Hg, Tl, and blood Pb; v) risk assessment by generating hazard quotients (HQs) for the single metal and hazard index (HI) for the co-occurrence of metals. Eighteen metals in urine and Pb in blood were determined by sector field inductively coupled plasma mass spectrometry. Metal concentrations were comparable with RVs reported in other countries, except for slightly higher As, Be, Ir, Pd, Pt, Rh, and Tl levels. Smoking was associated with Cd; age with Pb; drinking bottled water with As and Cd; consumption of fish with As and Hg; amalgams with Hg and Sn; dental restorations with Pd and Pt; use of jewelry with Co and Rh, and piercing with Ni. While HQs for urine Cd, Hg, Tl and blood Pb suggested that adverse effects were unlikely, the HQ value raised the question of whether additive interactions of these metals could produce health concern. The obtained HBM data can be an early warning for accumulations of metals and identification of subgroups at risk.

Targeted next-generation sequencing of cancer genes in advanced stage malignant pleural mesothelioma: a retrospective study.

INTRODUCTION: Malignant pleural mesothelioma (MPM) is a rare malignant disease, and the understanding of molecular pathogenesis has lagged behind other malignancies. METHODS: A series of 123 formalin-fixed, paraffin-embedded tissue samples with clinical annotations were retrospectively tested with a commercial library kit (Ion AmpliSeq Cancer Hotspot Panel v.2, Life Technologies, Grand Island, NY) to investigate 50 genes plus other two, BRCA1-associated protein-1 (BAP-1) and neurofibromatosis-2 (NF2), frequently altered in MPM. DNA was obtained from tissues after manual microdissection and enriched for at least 50% cancer cells. Variations affecting protein stability or previously correlated to cancer, more frequently identified (≥ 25 patients with at least 10% of allelic frequency), were subsequently evaluated by Sanger sequencing. Immunohistochemistry staining for BAP1 and NF2 proteins was also performed. RESULTS: The commonest genetic variations were clustered in two main pathways: the p53/DNA repair (TP53, SMACB1, and BAP1) and phosphatidylinositol 3-kinase-AKT pathways (PDGFRA, KIT, KDR, HRAS, PIK3CA, STK11, and NF2). PIK3CA:c.1173A>G mutation, STK11:rs2075606 (T>C), or TP53:rs1042522 (Pro/Pro) was significantly associated with time to progressive disease (TTPD; all p values < 0.01). Furthermore, the accumulation of genetic alterations correlated with shorter TTPD and reduced overall survival (TTPD p value = 0.02, overall survival p value = 0.04). BAP1 genetic variations identified were mainly located in exons 13 and 17, and BAP1 nonsynonymous variations were significantly correlated with BAP1 protein nuclear localization. CONCLUSION: Next-generation sequencing was applied to a relatively large retrospective series of MPM using formalin-fixed, paraffin-embedded archival material. Our results indicate a complex mutational landscape with a higher number of genetic variations in the p53/DNA repair and phosphatidylinositol 3-kinase pathways, some of them with prognostic value.

Health Impact Assessment practice and potential for integration within Environmental Impact and Strategic Environmental Assessments in Italy.

Avoiding or minimizing potential environmental impact is the driving idea behind protecting a population's health via Environmental Impact Assessments (EIAs) and Strategic Environmental Assessments (SEAs). However, both are often carried out without any systematic approach. This paper describes the findings of a review of HIA, EIA andSEA experiences carried out by the authors, who act as institutional competent subjects at the national and regional levels in Italy. The analysis of how health is tackled in EIA and SEA procedures could support the definition of a protocol for the integration of HIA with EIA and SEA. Although EIA and SEA approaches include the aim of protecting health,significant technical and methodological gaps are present when assessing health systematically, and their basic principles regarding assessment are unsatisfactory for promoting and addressing healthcare concepts stated by the WHO. HIA is still poorly integrated into the decision-making process, screening and monitoring phases are only occasionally implemented, and operational details are not well-defined. The collaborative approach of institutions involved in environment and health is a core element in a systematic advancement toward supporting effective decisions and effective protection ofthe environment and health. At the Italian national level, the definition of guidelines and tools for HIA, also in relation with EIA and SEA, is of great interest.

[SENTIERI Project: rationale and objectives]. / Razionale e obiettivi del Progetto SENTIERI.

The Istituto Superiore di Sanità (National Institute of Health-ISS), in partnership with a network of Italian national and regional scientific institutions, initiated the SENTIERI Project (Epidemiological Study of Residents in Italian Contaminated Sites-NPCSs), the objectives, methods and initial results of which were published by Epidemiologia & Prevenzione in 2010 and 2011. In the course of 2013, some of the SENTIERI Project findings were published in international scientific journals, and the "SENTIERI approach" was among those sanctioned by the World Health Organization to conduct an initial description of the health status of residents of contaminated sites. The present Report, set up jointly by ISS and the Italian Network of Cancer Registries (AIRTUM), as anticipated in the 2011 Report, aims to provide, for each of the 18 National Priority Contaminated Sites included in the SENTIERI Project where the Italian Association of Cancer Registries is active, a mortality update to 2010, analyses of cancer incidence (1996-2005 in 17 NPCSs) and of hospital discharges (2005-2010), as is explained in detail in Chapter 2, pertaining to the project's materials and methods. The results of the analyses for each NPCS are presented in Chapter 3, while Chapter 4 includes a critical appraisal, a discussion of the methodological approach and a series of concluding remarks. The second section of the Report takes an in-depth look at important issues of public health and scientific research in contaminated sites. This Report represents an important step towards implementing a permanent epidemiological surveillance system in Italy's contaminated sites, the ultimate goal of the SENTIERI Project.

[SENTIERI Project: discussion and conclusions]. / Discussione e conclusioni del Progetto SENTIERI.

The SENTIERI Project represents the first comprehensive analysis of the health impact of residence in National Priority Contaminated Sites (NPCSs). For the first time, it considers three distinct health outcomes: mortality (2003-2010), cancer incidence (1996- 2005) and hospital discharges (2005-2010). The Report includes a commentary explaining methodology and approach, as well as remarks on the causal association between environmental exposures and investigated health outcomes based on the a priori assessments of the epidemiological evidence; the main implications for public health and scientific research priorities are also presented. The approach put forward by SENTIERI was among those sanctioned by the World Health Organization to conduct an initial description of the health status of residents of contaminated sites. Results relating to individual diseases that can be traced back to a single agent, such as asbestiform fibres, can be easily analysed. The Biancavilla NPCS (where the fluoro-edenite asbestiform fibre was found) displays excesses of pleural mesothelioma and its proxy, malignant pleural tumours, as does Priolo, where asbestos coexists with other pollutants. Increased risk was also recorded in NPCSs adjacent to the coast hosting harbour areas (such as Trieste, Taranto and Venice) or comprising industrial areas specialising in the production of chemicals (Laguna di Grado e Marano, Priolo and Venezia) and steel (Taranto, Terni, Trieste). Increases of pathologies, such as cancer and respiratory diseases, connected to more than one agent, in industrial sites with multiple and diverse sources of exposures, prove harder to interpret. There are also more complex cases in which results do not appear consistent in the three databases or by gender (such as lung cancer in Venice, where mortality and hospital discharges have only increased among women). In order to adequately examine these we must consider factors such as the appropriateness of the health outcome showing the increase, considering latency and the length of the observation period. Of further interest are results relating to diseases of the urinary tract such as kidney failure in the NPCSs of Basso bacino del fiume Chienti, Taranto, Milazzo and Priolo. Overall, the results discussed above are consistent with the previous findings pertaining to mortality for 1995-2002. The present analysis also introduces a new element - the study of cancer incidence and hospital discharges - which can tell us a great deal about diseases with high survival rates or non lethal ones. The first is the case of thyroid cancer, which presents increases in both databases and for both genders in a number of NPCSs (Brescia-Caffaro, Laghi di Mantova, Milazzo, Sassuolo- Scandiano and Taranto). The study of cancer incidence and hospital discharges also revealed cancer excesses for melanoma, breast cancer and non Hodgkin lymphoma in Brescia-Caffaro NPCS where PCBs (Polychlorinated biphenyl) are the site's main pollutant. PCBs, according to the 2013 evaluation of the International Agency for Research on Cancer, are ascertained human carcinogens for melanoma and probable carcinogens for breast cancer and non-Hodgkin lymphoma. The results pertaining to cancer incidence in the 17 NPCSs can also be presented using rankings by area or disease analyzed by a multivariate hierarchical Bayesian model. These rankings reveal an overlapping of credibility intervals, such that it is not possible to speak of a limited number of cancer sites or of certain NPCSs as being particularly affected. Every NPCS, therefore, must be considered individually and ordering them by ranking of cancer incidence wouldn't be appropriate. Data collected concerning some of the NPCSs in the context of the SENTIERI Project is so conclusive that remediation measures can immediately be put in place. This is the case in the Biancavilla and Brescia-Caffaro NPCSs. A similar conclusion can be drawn for complex locations such as Taranto, where, based on the results of SENTIERI Projects and the whole available information, we can safely conclude that exposure to environmental agents played an important role, allowing us to set in place 'Integrated evaluation of environmental and health impact procedures'. SENTIERI approach does not allow definitive causal assessments. However, as stated above, these results do provide a topic for further study without getting in the way of initiatives promoting urgent environmental remediation.

The fibres with fluoro-edenitic composition in Biancavilla (Sicily, Italy): health impact and clues for environmental remediation.

Subsequently to the observation of a localized excess of mortality from malignant pleural neoplasms in the town of Biancavilla (Sicily), previously unknown amphibolic fibres with fluoro-edenitic composition were detected as naturally occurring soil contaminants. Less then two years after the initial report, ISS provided a set of public health recommendations that were complied by regional and local institutions. The recognition of Biancavilla as a National Priority Contaminated Site in 2002 opened the way to clean-up interventions. An up-dating of epidemiological studies, exposure assessment investigations and in vivo and in vitro mechanistic studies on fluoro-edenite fibres is provided in this issue. Scientific evidence can provide a sound foundation to public health action and environmental remediation. Finally, it is now necessary to properly tune the response of the health system to the community needs in terms of diagnostic procedures and medical treatment.

PCDD/Fs and PCBs in ambient air in a highly industrialized city in northern Italy.

Ambient air samples were collected in five locations around a polychlorobiphenyl (PCB) production plant in a highly industrialized city in the north of Italy, for the analysis of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) and PCBs. PCDD/F atmospheric concentrations were lower than those generally detected in urban areas, while PCB concentrations were higher than in urban and industrialized areas in other countries, especially in the locations closest to the plant. To identify source emissions responsible for air pollution we used principal component analysis (PCA) to compare the "fingerprint" of the air in Brescia with some source-related experimental and published data. This analysis showed that the PCDD/F fingerprints were more similar to steel plant emission data, while none of the PCB air patterns were comparable to emission profiles, indicating that different sources are responsible for the concentration of these two pollutants. The highest PCB concentrations detected in the areas closest to the chemical plant are indicative of its impact on the surrounding environment.

[Environment and health in Taranto, southern Italy: epidemiological studies and public health recommendations]. / Ambiente e salute a Taranto: studi epidemiologici e indicazioni di sanità pubblica.

INTRODUCTION: in Taranto IPS (Italian polluted site, made up of 2 municipalities) the Decree defining site boundaries lists the presence of a refinery, a steel plant, a harbour area and waste landfills together with illegal dumping sites. Previous environmental and epidemiological investigations in the area documented the presence of environmental contamination and increased mortality from respiratory and cardiovascular diseases as well as a number of cancer sites; for these same health outcomes the cohort study of residents showed increased risk both in terms of mortality and morbidity. OBJECTIVE: to describe the health status of residents in Taranto IPS analyzing different health indicators available at municipal level, i.e. mortality (2003-2009), mortality time trend (1980-2008) and cancer incidence (2006-2007). METHODS: the analyses were carried out for residents in Taranto IPS. Mortality update (SENTIERI Project, 2003-2009) regards 63 single or grouped causes (all ages, both genders); for a selection of causes 0-1 and 0-14 age classes were analyzed (both genders combined). Standardized mortality ratio crude (SMR) and deprivation adjusted together with 90% confidence intervals (90%CI) were computed using regional rates for comparison. Mortality time trend (1980-2008, triennial intervals) were analyzed calculating standardized rates (0-99 years, both genders, per 100,000, Italian population at 2001 Census as reference) and 90%CI. Time trends were computed for all causes, all neoplasms (and lung cancer), cardiovascular diseases (and ischemic heart diseases), respiratory diseases (also acute and chronic) and all causes infant mortality (both genders combined). For cancer incidence (2006-2007) Standardized incidence ratio (SIR) and 90%CI were calculated for both genders; incidence rates of cancer registries of the macroarea South and Islands (2005-2007) and rates of Taranto Province excluding SIN municipalities (2006-2007) were used for comparison. RESULTS: in Taranto IPS mortality among men is in excess in both periods (SENTIERI Project 1995-2002 and 2003-2009) for all causes, all neoplasms (including lung and pleural cancer), dementia, cardiovascular diseases (including hypertension and ischemic heart diseases), respiratory diseases (including the acute ones) and digestive diseases (including liver cirrhosis). All causes infant mortality is in excess in both periods. Time trends show that Taranto IPS rates are higher than regional average in the majority of time intervals for most causes in both genders. Rates are often higher than national average form any triennial intervals. Among males, over the whole period, mortality in Taranto IPS is higher than regional and national average for causes as lung cancer, diseases of the respiratory system, including the chronic ones. Among females, since the early Nineties, lung cancer and ischemic heart diseases are in excess in Taranto IPS. Also infant mortality is higher for the whole period in Taranto IPS than regional and national averages. Cancer incidence results show excesses for cancer sites already indicated by mortality data. CONCLUSIONS: mortality analyzed in the context of SENTIERI Project (1995-2002 and 2003-2009), time trend mortality (1980-2008) and cancer incidence (2006- 2007) show, in both genders, excesses for causes for which an etiologic role of environmental exposure present in Taranto IPS are either ascertained or suspected on the basis of a priori evaluation of the epidemiological evidence. The finding of excess infant mortality is of the utmost importance in public health terms. Most diseases showing an increased risk have multifactorial etiology, therefore interventions of proven efficacy, such as smoking cessation, food education, measures for cardiovascular risk reduction and breast cancer and colon screening programmes should be planned. To build a climate of confidence and trust between citizens and public institutions study results and public health actions are to be communicated objectively and transparently.

[SENTIERI Project: rationale and objectives]. / Razionale e obiettivi del Progetto SENTIERI.

SENTIERI Project (Mortality study of residents in Italian polluted sites) studied mortality of residents in the sites of national interest for environmental remediation (Italian polluted sites--IPSs). IPSs are in proximity of either active or dismissed industrial areas, near dumping sites of industrial and hazardous waste or incinerators. SENTIERI Project described and evaluated the mortality of the populations residing in IPSs and it specifically focused on causes of death for which environmental exposure is suspected or ascertained to play an etiologic role. The epidemiological evidence of the causal association was classified a priori into one of these three categories: Sufficient (S), Limited (L) and Inadequate (I). The study results will allow the priorities setting in remediation intervention, so as to prevent adverse health effects from environmental exposure. At the time of 2001 Census, about 10%of Italian population resided in the 44 IPSs included in SENTIERI; the mortality analysis was carried out for the years 1995-2002 for 63 causes of death. The study results for the 44 IPSs are here commented and read on the basis the a priori evaluation of the epidemiological evidence in terms of strength of the causal association, and taking into account the limits of a geographic study design and its implied complexities. The procedures and results of the evidence evaluation have been presented in a 2010 Supplement of Epidemiology & Prevention devoted to SENTIERI.

[Global burden of mortality in Italian polluted sites]. / Valutazioni globali del carico di mortalità nei siti di interesse nazionale per le bonifiche.

SENTIERI Project has assessed the overall mortality profile in all the IPSs combined, and performed IPS-specific analyses. The epidemiological evidence of the causal association between cause of death and exposure was classified into one of these three categories: Sufficient (S), Limited (L) and Inadequate (I). The procedures and results of the evidence evaluation have been presented in a 2010 Supplement of Epidemiology & Prevention devoted to SENTIERI. Mortality for causes of death with a priori Sufficient or Limited evidence of association with the environmental exposure exceeds the expected figures, with a SMR of 115.8 for men (90%CI 114.4-117.2; 2 439 extra deaths) and 114.4 for women (90% CI 112.4-116.5; 1 069 extra deaths). These excesses are also observed when analysis is extended to all the causes of death (i.e. with no restriction to the ones with a priori Sufficient or Limited evidence): for a total of 403 692 deaths (men and women combined), an excess of 9 969 deaths is observed, with an average of around 1 200 extra deaths per year. Most of these excesses are observed in IPSs located in Southern and Central Italy. The distribution of the causes of deaths shows that the excesses are not evenly distributed: cancer mortality accounts for 30%of all deaths, but is 43.2%of the excess deaths (4 309 cases of 9 969). Conversely, the percentage of excesses in non cancer causes, 19%, is lower than their share of total mortality (42%). Consistently with previous studies, the results suggest that the health status of populations living in the IPSs is worse than what regional averages show. Compared to previous studies, the analysis of the causes selected in SENTIERI, on the basis of a priori Sufficient or Limited evidence of association with the environmental exposures, provides additional information on their role, though some limitations, due to methodology and data used, should be considered.

[SENTIERI Project: discussion and conclusions]. / Progetto SENTIERI: discussione e conclusioni.

SENTIERI Project is the first comprehensive study of the health impact of residence in Italian polluted sites (IPSs). The present Chapter examines the main validity aspects of the present mortality investigation and the evaluation of causality of the observed associations; in addition, some recommendations for public health intervention and research priorities in epidemiological studies on environment and health are given. Exposure ascertainment is a key aspect when an ecological study design is adopted in environmental epidemiology, therefore any exposure potentially affecting the population at study should be described in detail. This is here discussed. SENTIERI is an ecological study, based on a priori hypotheses, in which each IPS's types of exposure were described with specific attention to human exposure. Though, when commenting the results, the problem of concurrent air pollution exposure and/or industrial activities implying occupational risk, if present in the IPSs, was taken into account. Socioeconomic status is a determinant of health and disease, therefore in SENTIERI the Standardized Mortality Ratios were computed both crude and adjusted for an ad hoc deprivation index. About 60% versus an expected 40% of IPSs residents are in the two most deprived quintiles of the index. This hints to a possible problem of environmental justice that should be taken into account when planning remediation intervention. The mortality results here presented are a first step in the epidemiological IPSs' characterization, and some developments have been made or planned. Firstly, a mortality analysis was performed combining mortality data in IPSs presenting similar pollution, i.e. asbestos, or industrial hazardous wastes or dumping sites; secondly, the mortality analysis will be extended beyond 2002, namely the year when ICD X started to be in use in Italy. In addition, disease prevalence will be investigated using hospital discharge records; cancer incidence and congenital anomalies incidence will be studied in IPSs in which a Cancer Register or a Congenital Anomalies Register are active. The above described activities will lead to a more valid estimate of the disease burden of IPSs residents, and allow to identify priorities of remediation activities. The method adopted in SENTIERI, specifically the ecological design and the use of mortality data at municipal level, in general does not grant the evaluation of the causal association between environmental exposure and adverse health effects. However, it allows etiological observations that make unacceptable the delay of remediation intervention.

The impact measure of solid waste management on health: the hazard index.

The risk associated with waste exposure depends on the level of emissions arising from waste disposal and from the effects of these emissions on human health (dose-response). In 2007 an epidemiological study was conducted in two Italian provinces of the Campania Region, namely Naples and Caserta, with the aim of assessing the health effects deriving from exposure to waste. In these studies, the important aspect is the population exposure assessment, in relation to the different types of waste disposal. The Regional Agency for Environmental Protection (ARPA Campania) has identified and characterized the various authorized/unauthorized dumping sites in the provinces of Naples and Caserta. Most of the waste disposal used are illegal and invisible (sunken or buried); thus, the toxic substances therein contained are unknown and difficult to identify. In order to locate the possible areas exposed to a higher waste-related health risk, a synthetical "hazard index" (at the municipality level) was designed. By means of GIS, the number of waste impact areas was identified for each of the 196 municipalities in the two provinces; then, Census data (ISTAT 2001) was used to estimate the proportion of the population living in the impact areas. The synthetical hazard index at municipality level accounts for three elements: a) the intrinsic characterization of the waste disposal, determining the way in which the pollutant is released; b) the impact area of the dumping site (within 1 km radius), same areas are influenced by more than one site; c) the density of the population living in the "impact area" surrounding the waste disposal site.

[Environment and health in Gela (Sicily): present knowledge and prospects for future studies]. / Ambiente e salute a Gela: stato delle conoscenze e prospettive di studio.

The study area includes the Municipalities of Gela, Niscemi and Butera located in the South of Sicily, Italy. In 1990 it was declared Area at High Risk of Environmental Crisis. In 2000 part of it was designated as Gela Reclamation Site of National Interest, RSNI. The site includes a private industrial area, public and marine areas, for a total of 51 km(2). Gela populationin 2008 was 77,145 (54,774 in 1961). Sea level:46 m. Total area: 276 km(2). Grid reference: 37 degrees 4' 0" N, 14 degrees 15' 0" E. Niscemi and Butera are located border to Gela. Populations are respectively 26,541 and 5,063. Sea level respectively: 332 m and 402 m. Close to the city of Gela, the industrial area, operating since 1962, includes chemical production plants, a power station and an oil refinery plant, one of the larger in Europe, refining 5 millions tons of crude per year. From the beginning the workforces decreased from 7,000 to the current 3,000 units. Over the years, these industrial activities have been a major source of environmental pollution. Extremely high levels of toxic, persistent and bio-accumulating chemical pollutants have been documented. Many relevant environmental and health data are available. Prior to the studies described in the present publication, their use in order to identify environmental pressures on health has been limited. Nevertheless, since several years different epidemiological studies have provided evidence of the occurrence of health outcomes significantly higher than in neighbouring areas and compared to regional data. In 2007 a Multidisciplinary Working Group has been established, to analyze the existing data on pollution-exposure-effect and to complete current knowledge on the cycle of pollutants, from migration in the environment to health impact. The present publication is a collection of contribution of this group of experts, supported by the following projects: Evaluation of environmental health impact and estimation of economic costs at of National Interest Remediation Sites coordinated by the Italian National Institute of Health on behalf of the Ministry for the Environment and Technical Assistance of WHO Health and Environment Centre to the Sicilian Region to develop plans for environmental remediation. Results describe the state of contamination of a variety of environmental matrices in the area. Other contributions are addressed to understanding action mechanisms of main pollutants and their environmental pathways, as well as to identifying crucial knowledge to be used for studying the environment-health relations. A specific attention has been paid to pollutants migration in the environment and to the potential exposure of the population. Appropriate markers of exposure and physiological changes are described and referred to the chemical substances identified in the environment in Gela. Details are given about the genotoxic and endocrine disrupting potential, and about the potential association between markers of exposure and diseases observed in excess in the same area. Indications to develop specific biomarkers for Index Substances and human biomonitoring surveys for populations exposed to environmental risk are presented and discussed. A specific multiple-exposure risk assessment procedure is proposed for Index Substances. Epidemiological studies useful to describe the health status of Gela population are summarized. One report deals with the occupational and residential analyses of male petrochemical workers, born in Sicily, employed from 1960 to the end of 1993, followed up for mortality from 1960 to 2002. Major findings were amarked healthy worker effect and an increased lung cancer risk for residence in Gela. The analyses of death certificates from 1995 to 2002 and of hospital discharge records from 2001 to 2007 confirm the potentialities of these current statistics for ecological studies: they depict the poor health conditions of Gela residents compared to other neighbouring municipalities in a 40-km range. Infact, the overall mortality rate for tumor and non-tumor causes in Gela is significantly higher for both sexes, and this is shown also in the Municipality of Niscemi, especially among the male population. Hospital discharge records for tumor causes, but especially for non-tumor ones, exceeded expectations in both genders and must be analysed taking into consideration the attraction exerted on the surrounding areas by the Gela hospital. Data analysis according to 5 ten-year birth cohorts, from 1915 to 1964, shows a decreasing mortality trend, whereas the increase of hospital admissions is confirmed in the younger generations. The issue of birth defects is recurrent in this area: a suitable register is lacking so that updated figures cannot be presented. However, data previously published showed excesses of prevalence rates of several specific birth defects, mainly urinary tract and genital anomalies. The same is worth in the incidence of new cancer cases since the development of a proper register is yet in progress. Tools and methodologies that should be applied in Gela to study environment-health relations are proposed, like Life Cycle Analysis, dispersion patterns and an air-quality monitoring system. A conceptual model considering all pollution sources and different exposure patterns present in Gela, developed by the Multidisciplinary Working Group, is presented. Among the activities carried out by regional authorities, two Reports on the Regional Environment Protection Agency monitoring activity and on the EU Program SEARCH, School Environment And Respiratory Health in Children, are included. A section is devoted to understanding what is necessary to build an epidemiological monitoring system specifically designed for this area, in order to keep under permanent control environment-related health outcomes. This includes a systematic and continuative collection, storage and analysis of environmental-induced diseases, exposure and risk factors, as well as a timely dissemination of those information to the decision-makers. The final article describes the research activities carried out to design and implement a human biomonitoring survey in the area. These activities included relation-building with local communities, information collection, meetings, involvement of stake-holders. This experience will reach its climax when the community-exposure data feedback will be provided, because it will mark the consolidation of present knowledge and its possible processing into public health action plans. The present publication can represent an important tool and a model for all interest-bearers to assess environmental pollution impacts on human health in contaminated areas. A local system to assess the relation between environmental pollution and population health is therefore urgently needed to provide risk managers with ad-hoc tools to improve environmental protection and prevent further risks for local communities.