BACKGROUND: the mixed and complex nature of industrially contaminated sites (ICSs) leads to heterogeneity in exposure and health risk of residents living nearby. Health, environment, and social aspects are strongly interconnected in ICSs, and local communities are often concerned about potential health impact and needs for remediation. The use of human biomonitoring (HBM) for impact assessment of environmental exposure is increasing in Europe. The COST Action IS1408 on Industrially Contaminated Sites and Health Network (ICSHNet) decided to reflect on the potential and limitations of HBM to assess exposure and early health effects associated with living near ICSs. OBJECTIVES: to discuss challenges and lessons learned for addressing environmental health impact near ICSs with HBM in order to identify needs and priorities for HBM guidelines in European ICSs. METHODS: based on the experience of the ICSHNet research team, six case studies from different European regions that applied HBM at ICSs were selected. The case studies were systematically compared distinguishing four phases: the preparatory phase; study design; study results; the impact of the results at scientific, societal, and political levels. RESULTS: all six case studies identified opportunities and challenges for applying HBM in ICS studies. A smart choice of (a combination of) sample matrices for biomarker analysis produced information about relevant time-windows of ex posure, which matched with the activities of the ICSs. Combining biomarkers of exposure with biomarkers of (early) biological effects, data from questionnaires or environmental data enabled fine-tuning of the results and allowed for more targeted remediating actions aimed to reduce exposure. Open and transparent communication of study results with contextual information and involvement of local stakehold ers throughout the study helped to build confidence in the study results, gained support for remediating actions, and facilitated sharing of responsibilities. Using HBM in these ICS studies helped in setting priorities in policy actions and in further research. Limitations were the size of the study population, difficulties in recruiting vulnerable target populations, availability of validated biomarkers, and coping with exposure to mixtures of chemicals. CONCLUSIONS: based on the identified positive experiences and challenges, the paper concludes with formulating recommendations for a European protocol and guidance document for HBM in ICS. This could advance the use of HBM in local environmental health policy development and evaluation of exposure levels, and promote coordination and collaboration between researchers and risk managers.
SENTIERI Project (Mortality study of residents in Italian polluted sites) studies mortality of residents in the sites of national interest for environmental remediation (Italian polluted sites, IPS). IPSs are located in the vicinity of industrial areas, either active or dismissed, near incinerators or dumping sites of industrial or hazardous waste. SENTIERI includes 44 out of 57 sites comprised in the "National environmental remediation programme". For each IPS contamination data were collected, both from the national and local environmental remediation programmes. Contamination data are mainly for private industrial areas; municipal and/or green and agricultural areas were poorly studied, therefore it is difficult to assess the environmental exposure of populations living inside and/or near IPSs. Each one of 44 SENTIERI IPSs includes one or more municipalities. Mortality in the period 1995-2002 was studied for 63 single or grouped causes at municipality level computing: crude rate, standardized rate, standardized mortality ratios (SMR), and SMR adjusted for an ad hoc deprivation index. Regional populations were used as reference for SMR calculation. The deprivation index was constructed using 2001 national census variables on the following socioeconomic domains: education, unemployment, dwelling ownership and overcrowding. A characterizing element of SENTIERI Project is the a priori evaluation of the epidemiological evidence of the causal association between cause of death and exposure. Exposures for which epidemiological evidence was assessed are divided into IPSs environmental exposures and other exposures. The former are defined on the basis of the decrees defining sites' boundaries; they are coded as chemicals, petrochemicals and refineries, steel plants, power plants, mines and/or quarries, harbour areas, asbestos or other mineral fibres, landfills and incinerators. The other exposures, considered for their ascertained adverse health effects are: air pollution, active and passive smoking, alcohol intake, occupational exposure and socioeconomic status. The epidemiologists in SENTIERI Working Group (WG) developed a procedure to examine the epidemiological literature published from 1998 to 2009; the WG identified a hierarchy in the literature examined to classify each combination of cause of death and exposure in terms of strength of causal inference. The selected epidemiological information included primary sources (handbooks and Monographs and Reports of international and national scientific institutions), statistical re-analyses, literature reviews, multi-centric studies and single investigations. This hierarchy relies on the epidemiological community consensus, on assessments based on the application of standardized criteria, weighting the studies design and the occurrence of biased results. Therefore, to put forward the assessment, the criteria firstly favoured primary sources and quantitative meta-analyses and, secondly, consistency among sources. The epidemiological evidence of the causal association 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 Epidemiologia & Prevenzione devoted to SENTIERI. SENTIERI studied IPS-specific mortality and the overall mortality profile in all the IPSs combined. Some IPS-specific results are noteworthy and are herementioned. The presence of asbestos (or asbestiform fibres in Biancavilla) was the motivation for including six IPSs (Balangero, Emarese, Casale Monferrato, Broni, Bari-Fibronit, Biancavilla) in the "National environmental remediation programme". In these sites (with the only exception of Emarese) increases in malignant pleural neoplasm mortality were observed, in four of them the excess was in both genders. In six other sites (Pitelli, Massa Carrara, Aree del litorale vesuviano, Tito, Area industriale della Val Basento, Priolo), in which additional sources of environmental pollution were reported, mortality from malignant pleural neoplasm was increased in both genders in Pitelli, Massa Carrara, Priolo and Litorale vesuviano. In the twelve sites where asbestos was mentioned in the decree, a total of 416 extra cases of malignant pleural neoplasms were computed. Asbestos and pleural neoplasm represent an unique case. Unlike mesothelioma, most causes of death analyzed in SENTIERI have multifactorial etiology, furthermore in most IPSs multiple sources of different pollutants are present, sometimes concurrently with air pollution from urban areas: in these cases, drawing conclusions on the association between environmental exposures and specific health outcomes might be complicated. Notwithstanding these difficulties, in a number of cases an etiological role could be attributed to some environmental exposures. The attribution could be possible on the basis of increases observed in both genders and in different age classes, and the exclusion of a major role of occupational exposures was thus allowed. For example, a role of emissions fromrefineries and petrochemical plants was hypothesized for the observed increases in mortality from lung cancer and respiratory diseases in Gela and Porto Torres; a role of emissions frommetal industries was suggested to explain increased mortality from respiratory diseases in Taranto and in Sulcis-Iglesiente-Guspinese. An etiological role of air pollution in the raise in congenital anomalies and perinatal disorders was suggested in Falconara Marittima, Massa-Carrara,Milazzo and Porto Torres. A causal role of heavy metals, PAH's and halogenated compounds was suspected for mortality from renal failure in Massa Carrara, Piombino, Orbetello, Basso Bacino del fiume Chienti and Sulcis-Iglesiente- Guspinese. In Trento-Nord, Grado and Marano, and Basso bacino del fiume Chienti increases in neurological diseases, for which an etiological role of lead, mercury and organohalogenated solvents is possible, were reported. The increase for non- Hodgkin lymphomas in Brescia was associated with the widespread PCB pollution. SENTIERI Project assessed also the overall mortality profile in all the IPSs combined. The mortality for causes of death with a priori Sufficient or Limited evidence of causal association with the environmental exposure showed 3 508 excess deaths for all causes, corresponding to 439 per year; the number of excess deaths was 1 321 for respiratory diseases, 898 for lung cancer and 588 for pleural neoplasms. When considering excess mortality with no restriction to causes of death with a priori Sufficient or Limited evidence of causal association with the environmental exposure, the number of excess deaths for all causes was 9 969 (SMR 102.5, about 1 200 excess deaths per year; the excess was 4 309 for all neoplasms (SMR 103.8, about 538 excess deaths per year), 1 887 for circulatory systemdiseases, and 600 for respiratory systemdiseases. Most of these excesses were observed in IPSs located in Southern and Central Italy. The distribution of the causes of deaths showed that the excesses are not evenly distributed: cancer mortality accounts for 30% of all deaths, but it is 43.2% of the excess deaths (4 309 cases out of 9 969). Conversely, the percentage of excesses in noncancer causes is 19%, while their share of total mortality is 42%. SENTIERI is affected by some limitations, such as the ecological study design and a time window of observation possibly inappropriate to account for induction-latency time; the analyzed outcome (mortality instead than incidence) might be unsuitable as well. Despite its limitations, SENTIERI documented increased mortality for single IPSs and an overall burden of disease in residents in Italian polluted sites. These excesses could be attributed to multiple risk factors, that include also the environmental exposures. The study results will be shared with the Ministries of Health and Environment, Regional governments, Regional environmental protection agencies, Local health authorities and municipalities. A collaborative approach between institutions in charge of environmental protection and health promotion will foster, among else, a scientifically sound and transparent communication process with concerned populations. ; Il Progetto SENTIERI (Studio Epidemiologico Nazionale dei Territori e degli Insediamenti Esposti a Rischio da Inquinamento) riguarda l'analisi della mortalit? delle popolazioni residenti in prossimit? di una serie di grandi centri industriali attivi o dismessi, o di aree oggetto di smaltimento di rifiuti industriali e/o pericolosi, che presentano un quadro di contaminazione ambientale e di rischio sanitario tale da avere determinato il riconoscimento di "siti di interesse nazionale per le bonifiche" (SIN). Lo studio ha preso in considerazione 44 dei 57 siti oggi compresi nel "Programma nazionale di bonifica", che coincidono con i maggiori agglomerati industriali nazionali; per ciascuno di essi si ? proceduto a una raccolta di dati di caratterizzazione, e successivamente a una loro sintesi. La maggior parte dei dati raccolti proviene dai progetti di bonifica ipotizzati per i diversi siti, da cui si evince che oggetto di caratterizzazione e di valutazione del rischio sono state prevalentemente le aree private industriali, quelle, cio?, ritenute causa delle diverse tipologie di inquinamento (definite in SENTIERI esposizioni ambientali). Le aree pubbliche cittadine e/o a verde pubblico e le aree agricole comprese all'interno dei SIN sono state poco investigate. I SIN studiati sono costituiti da uno o pi? Comuni. La mortalit? ? stata studiata per ogni sito, nel periodo 1995-2002, attraverso i seguenti indicatori: tasso grezzo, tasso standardizzato, rapporto standardizzato di mortalit? (SMR) e SMR corretto per un indice di deprivazione socioeconomica messo a punto ad hoc. Nella standardizzazione indiretta sono state utilizzate come riferimento le popolazioni regionali. L'indice di deprivazione ? stato calcolato sulla base di variabili censuarie appartenenti ai seguenti domini: istruzione, disoccupazione, propriet? dell'abitazione, densit? abitativa. Gli indicatori di mortalit? sono stati calcolati per 63 cause singole o gruppi di cause. La presenza di amianto (o di fibre asbestiformi a Biancavilla) ? stata la motivazione esclusiva per il riconoscimento di sei SIN (Balangero, Emarese, Casale Monferrato, Broni, Bari-Fibronit e Biancavilla). In tutti i siti (con l'esclusione di Emarese) si sono osservati incrementi della mortalit? per tumore maligno della pleura e in quattro siti i dati sono coerenti in entrambi i generi. In sei siti con presenza di altre sorgenti di inquinamento oltre all'amianto, la mortalit? per tumore maligno della pleura ? in eccesso in entrambi i generi a Pitelli, Massa Carrara, Priolo e nell'Area del litorale vesuviano. Nel periodo 1995-2002 nell'insieme dei dodici siti contaminati da amianto sono stati osservati un totale di 416 casi di tumore maligno della pleura in eccesso rispetto alle attese. Quando gli incrementi di mortalit? riguardano patologie con eziologia multifattoriale, e si ? in presenza di siti industriali con molteplici ed eterogenee sorgenti emissive, talvolta anche adiacenti ad aree urbane a forte antropizzazione, rapportare il profilo di mortalit? a fattori di rischio ambientali pu? risultare complesso. Tuttavia, in alcuni casi ? stato possibile attribuire un ruolo eziologico all'esposizione ambientale associata alle emissioni di impianti specifici (raffinerie, poli petrolchimici e industrie metallurgiche). Tale attribuzione viene rafforzata dalla presenza di eccessi di rischio in entrambi i generi, e in diverse classi di et?, elementi che consentono di escludere ragionevolmente un ruolo prevalente delle esposizioni professionali. Per esempio, per gli incrementi di mortalit? per tumore polmonare e malattie respiratorie non tumorali, a Gela e Porto Torres ? stato suggerito un ruolo delle emissioni di raffinerie e poli petrolchimici, a Taranto e nel Sulcis-Iglesiente-Guspinese un ruolo delle emissioni degli stabilimenti metallurgici. Negli eccessi di mortalit? per malformazioni congenite e condizioni morbose perinatali ? stato valutato possibile un ruolo eziologico dell'inquinamento ambientale a Massa Carrara, Falconara, Milazzo e Porto Torres. Per le patologie del sistema urinario, in particolare per le insufficienze renali, un ruolo causale di metalli pesanti, IPA e composti alogenati ? stato ipotizzato a Massa Carrara, Piombino, Orbetello, nel Basso bacino del fiume Chienti e nel Sulcis-Iglesiente-Guspinese. Incrementi di malattie neurologiche per i quali ? stato sospettato un ruolo eziologico di piombo, mercurio e solventi organo alogenati sono stati osservati rispettivamente a Trento Nord, Grado e Marano e nel Basso bacino del fiume Chienti. L'incremento dei linfomi non-Hodgkin a Brescia ? stato messo in relazione con la contaminazione diffusa da PCB. Ulteriori elementi di interesse sono stati forniti dalle stime globali della mortalit? nell'insieme dei siti oggetto del Progetto SENTIERI. In particolare, ? emerso che la mortalit? in tutti i SIN, per le cause di morte con evidenza a priori Sufficiente o Limitata per le esposizioni ambientali presenti supera l'atteso, con un SMR di 115.8 per gli uomini (IC 904.4-117.2, 2 439 decessi in eccesso) e 114.4 per le donne (IC 902.4-116.5; 1 069 decessi in eccesso). Tale sovramortalit? si riscontra anche estendendo l'analisi a tutte le cause di morte, cio? non solo per quelle con evidenza a priori Sufficiente o Limitata: il totale dei decessi, per uomini e donne, ? di 403 692, in eccesso rispetto all'atteso di 9 969 casi (SMR 102.5%; IC 902.3-102.8), con una media di oltre 1 200 casi annui. Si ritiene opportuno ricordare che il Progetto SENTIERI, per obiettivi, disegno e metodi, rappresenta uno strumento descrittivo che verifica, in prima istanza, se e quanto il profilo di mortalit? delle popolazioni che vivono nei territori inclusi in aree di interesse nazionale per le bonifiche si discosti da quello cause delle popolazioni di riferimento. Ai fini dell'interpretazione dei risultati, si ricorda che la presenza di eccessi di mortalit? pu? indicare un ruolo di esposizioni ambientali con un grado di persuasivit? scientifica che dipende dai diversi specifici contesti; invece, un quadro di mortalit? che non si discosti da quello di riferimento potrebbe riflettere l'assenza di esposizioni rilevanti, ma anche l'inadeguatezza dell'indicatore sanitario utilizzato (mortalit? invece di incidenza) rispetto al tipo di esposizioni presenti, o della finestra temporale nella quale si analizza la mortalit? rispetto a quella rilevante da un punto di vista dell'esposizione. La condivisione dei risultati con i ministeri della salute e dell'ambiente, le Regioni, le ASL, le ARPA e i Comuni interessati consentir? l'attivazione di sinergie fra le strutture pubbliche con competenze in materia di protezione dell'ambiente e di tutela della salute, e su questa base l'avvio di un processo di comunicazione con la popolazione scientificamente fondato e trasparente. Parole chiave: siti di interesse nazionale per le bonifiche (SIN), mortalit? geografica, impatto sanitario ambientale, Italia
