EXPOSURE ASSESSMENT OF PERSISTENT ORGANIC POLLUTANTS AND ASSOCIATED HEALTH RISKS AMONG ITALIAN POPULATION

I contaminanti organici persistenti costituiscono un gruppo di sostanze chimiche artificiali strutturalmente tra loro diverse e caratterizzate, quale elemento comune, da un\u2019elevata bio-persistenza e dalla capacit\ue0 di essere trasportate per lunghe distanze su scala planetaria, lontano dal luogo originario di emissione nell\u2019ambiente. A questa classe di sostanze chimiche appartengono, tra gli altri, i bifenili poli-clorurati, i pesticidi organo-clorurati, tra cui il DDT e i suoi metaboliti, e altri prodotti chimici come le dibenzo-p-diossine e i dibenzo-furani policlorurati. Queste sostanze chimiche sono ormai ampiamente distribuite nell'ambiente, in quanto alcuni di loro sono stati a lungo impiegati in agricoltura e nella sanit\ue0 pubblica come pesticidi (il DDT e gli altri insetticidi clorurati), altri come prodotti chimici industriali (i bifenili poli\u2013clorurati) e altri sono inevitabili sottoprodotti di processi industriali (le dibenzo-p-diossine e i dibenzo\u2013furani policlorurati). Per le loro caratteristiche tossicologiche, queste sostanze chimiche possono essere fonte di rischio per la salute umana. In Italia si \ue8 fatto largo uso di insetticidi della famiglia organo clorurata (DDT e prodotti simili) dagli anni \u201840 agli anni \u201870 del 1900, soprattutto per fini di salute pubblica, per l\u2019eradicazione di vettori (zanzare) della malaria e dei PCB, prodotti in Italia per il settore manifatturiero (produzione di dispositivi elettrici e termici), nella produzione di energia (uso di trasformatori e condensatori) e come materiali industriali in diversi comparti. Ci\uf2 nonostante, le informazioni sui livelli di esposizione della popolazione generale rimangono limitate. Questo studio si \ue8 proposto di misurare i livelli di alcuni insetticidi organo-clorurati e dei PCB nella popolazione generale italiana in tre luoghi diversi: Novafeltria (un paese del Centro Italia), Pavia (una citt\ue0 di medie dimensioni) e Milano (la seconda citt\ue0 pi\uf9 grande in Italia) e ad esplorare la relazione del loro accumulo nella popolazione con i luoghi di residenza, il sesso, l\u2019et\ue0 e la costituzione individuale. Per misurare le concentrazioni di PCB, i campioni di sangue sono stati raccolti campioni di sangue da 372 soggetti che hanno fornito il consenso informato e per misurare gli insetticidi organo-clorurati sono stati raccolti i campioni da 137 soggetti. Nel siero sono stati misurati 36 congeneri dei PCB e 8 insetticidi organo-clorurati mediante gas-cromatografia-spettrometria di massa. Per normalizzare le concentrazioni dei PCB e degli insetticidi organo-clorurati alle concentrazioni totali di lipidi nel sangue (una tecnica comunemente impiegata per tener conto del carattere lipofilico dei composti), sono stati misurate le concentrazioni sieriche di trigliceridi e colesterolo totale mediante tecniche standard di chimica clinica. Le informazioni personali quali il sesso, l'et\ue0, l'altezza e il peso, le abitudini alimentari, l'istruzione, la residenza e l'occupazione le informazioni sono state raccolte attraverso un questionario. Sono state impiegate analisi statistiche per evidenziare eventuali relazioni dei livelli degli analiti con caratteristiche dei soggetti indagati quali la residenza, l\u2019et\ue0, il sesso e l\u2019indice di massa corporea. Le concentrazioni degli analiti sono state indagate in termini sintetici per la popolazione complessiva dei 3 siti, e separatamente per i singoli siti, per sesso, per et\ue0 e per le categorie di BMI. I PCB congeneri 138, 153 e 180 sono stati quelli pi\uf9 frequentemente rilevati nei campioni e sono risultati quelli maggioritari nel concorrere alla dose totale di PCB. Il PCB 153 ha il pi\uf9 alto livello medio in ciascun sito. Il livello totale di PCB differisce in modo significativo tra questi siti (p < 0,0001) con concentrazioni mediane di 837, 1355 e 2062 pmol/g di lipidi, rispettivamente a Novafeltria, a Pavia e in Milano. Non sono state dimostrate differenze nella distribuzione dei livelli di PCB totali tra i due sessi. La somma dei PCB diossino-simili differiva in modo significativo (p < 0,0001) tra i siti (media 111 e 167 pmol/g di lipidi, rispettivamente) e tra i due sessi a Novafeltria e a Pavia (p = 0,011 e 0,009, rispettivamente). I PCB 138, 153, 170 e 180 differivano in modo significativo tra i luoghi di residenza (p < 0,0001), con valori pi\uf9 elevati nella popolazione di Milano. In generale, nella popolazione totale esaminata i livelli dei PCB totali e dei congeneri 138, 153, 156, 170 e 180 correlano positivamente con l'et\ue0 (coefficienti r di correlazione compresi tra 0,320 e 0,569, p < 0,0001). A Novafeltria i coefficienti r risultano compresi tra 0,545 e 0,670 e tra 0,516 e 0,666 a Pavia. A Milano, i coefficienti r per le correlazioni con et\ue0 sono risultati compresi tra 0,327 e 0,417 per i PCB totali e per i congeneri 138, 153 e 180. Ad eccezione del PCB 170 non \ue8 stata osservata alcuna differenza significativa nella distribuzione dei pi\uf9 abbondanti congeneri di PCB e PCB totali tra le diverse categorie di BMI (individui \u2018pi\uf9 o meno grassi\u2019). Tra gli insetticidi organo-clorurati, il p,p'-DDE e l\u2019HCB contribuiscono in misura magiore al carico corporeo totale per la classe di composti. I loro livelli differiscono in modo significativo tra le tre citt\ue0, con un trend di Milano > Novafeltria > Pavia (p < 0,0001). Considerando l\u2019intero campione, le femmine hanno concentrazioni significativamente pi\uf9 alte di HCB e p,p'-DDE rispetto ai maschi. Le concentrazioni di HCB sono significativamente pi\uf9 alte nelle femmine rispetto ai maschi di Milano (p = 0,029). Abbiamo osservato correlazioni positive tra la concentrazione di p,p'-DDE e HCB e l\u2019et\ue0 solo nei soggetti di Novafeltria (r = 0,468, p = 0,004). Considerando l\u2019intera popolazione studiata, le concentrazioni dell\u2019insetticida organo clorurati totali differiscono in modo significativo tra le categorie di BMI (p = 0,018). Abbiamo misurato il pattern dei principali congeneri dei PCB e degli insetticidi organo-clorurati in una campione abbastanza esteso della popolazione italiana. In generale il nostro studio fornisce informazioni sui livelli di esposizione a PCB e ad insetticidi organo-clorurati e fornisce indicazioni per ulteriori indagini.Persistent Organic Pollutants is a group of structurally diverse man-made chemicals characterized by a high bio-persistence and the ability to travel a long distance on the planetary scale. This class of chemicals includes polychlorinated biphenyls, organochlorinated pesticides such as DDT and its metabolites and other chemicals such as polychlorinated dibenzo-p-dioxins and polychlorinated dibenzo furans. These chemicals are widely distributed in the environment as some of them have long been employed in agriculture and in public health as pesticides, others as industrial chemicals and others are unavoidable by-products of industrial processes. These chemicals can be a source of health risk to human. Despite extensive use of OCPs such DDT in Italy in the 1940s to 1970s especially for public health control of malaria mosquitoes and PCBs in industry, in energy production and in industrial commodities, information on their exposure levels among the general population is limited. This study aims at determining the levels of OCPs and of PCB congeners among the residents from Italians living in three different places: Novafeltria (a village in Central Italy), Pavia (a mid-sized town) and Milan (the second-largest city in Italy) and at exploring the relationship with places of residence, gender, age and individual body size of their accumulation in the population. To measure PCBs concentrations, blood samples were collected from 372 consented subjects whereas to measure OCPs blood samples were collected from 137 subjects. Thirty six PCB congeners and eight OCPs were measured in blood serum by gas-chromatography-mass spectrometry. To normalize PCBs and OCPs concentrations to total blood lipid concentrations (a commonly employed technique to take into account the lipophilic character of the compounds), serum concentrations of triglycerides and total cholesterol were measured by standard clinical chemistry techniques. Personal information such as gender, age, height and weight, dietary habits, education, residence and occupation information were collected through a questionnaire. Statistical analyses were employed to highlight variation in analytes levels with respects to residence, age, gender and body mass index. The analytes concentrations were summarized for the overall population of three sites and separately for the individual sites, for gender, for age groups and for BMI categories. The PCB congeners 138, 153 and 180 were the most frequently detected in overall population sample and were the major contributors of total PCB burden. PCB 153 had the highest median level in each site. Total PCB level differed significantly between the study sites (p < 0.0001) with median concentrations of 837, 1355 and 2062 pmol/g lipid, respectively in Novafeltria, Pavia and Milan. No evidence was found for the difference in distribution of total PCB levels by genders. Total DL\u2013PCB differed significantly (p < 0.0001) between the sites (median 110, 51 and 167 pmol/g lipid, respectively) and genders of Novafeltria and Pavia (p = 0.011 and 0.009, respectively). PCB 138, 153, 170 and 180 differed significantly between the sites (p < 0.0001) with higher values in Milan population. In overall population total PCB, PCB 138, 153, 156, 170 and 180 correlated positively with age (r for linear correlations range between 0.320\u20130.569, p < 0.0001). In Novafeltria the r correlations range between 0.545\u20130.670 and 0.516\u20130.666 in Pavia. In Milan, r correlations with age range between 0.327\u20130.417 for total PCB, congener 138, 153 and 180. With exception of PCB 170 there was no evidence of significant difference in distribution of most abundant PCB congeners and total PCB across the BMI categories. Among the OCPs, p,p'-DDE and HCB were the most abundant and major contributors of total OCP concentration. Their levels differed significantly between the three towns with a trend Milan > Novafeltria > Pavia (p < 0.0001). Females had significantly higher concentrations of HCB and p,p'-DDE than males in overall population sample. HCB concentrations were significantly higher in females than in males of Milan (p = 0.029). We observed positive correlations of p,p'-DDE and HCB with age in Novafeltria subjects (r = 0.468, p = 0.004). Total OCP concentrations differed significantly across BMI categories (p = 0.018) in overall population. We have demonstrated a pattern of distribution of the levels of the main PCB congeners and OCPs in a fairly large population in Italy. Generally our study provides information on PCBs and OCPs exposure among the Italian general population and provides indications for further investigations

Persistent organochlorinated pesticides and mechanisms of their toxicity

Persistent organic pollutants comprised of organic chemicals like polychlorinated biphenyls, dibenzo-p-dioxins, dibenzofurans and organochlorinated pesticides which have many characteristics in common. Once released in the environment they resist physical, biological, chemical and photochemical breakdown processes and thus persist in the environment. They are subject to long transboundary air pollution transport. They accumulate in the food chain due to their lipophilicity, bioaccumulation and biomagnification properties. Human exposure occurs through inhalation of air, ingestion of food and skin contact. Because most of them bioaccumulate and remain preferentially in fat, their long-term effects are still a matter of public health concern. They are condemned for health adverse effects such as cancer, reproductive defects, neurobehavioral abnormalities, endocrine and immunological toxicity. These effects can be elicited via a number of mechanisms among others include disruption of endocrine system, oxidation stress and epigenetic. However most of the mechanisms are not clear thus a number of studies are ongoing trying to elucidate them. In this review, the underlying possible mechanisms of action and their possible roles in adverse developmental and reproductive processes are discussed and where possible a linkage is made to some existing epidemiological data. Both genomic and nongenomic pathways are used to describe these effects. Understanding of these mechanisms will enable development of strategies to protect the public by reducing these adverse effects. This review is limited to persistent organochlorinated pesticides (OCPs) such as dichlorodiphenyltrichloroethane (DDT) and its metabolites, hexachlorobenzene (HCB), beta-hexachlorocyclohexane (\u3b2-HCH) and endosulfan

Risk assessment of pesticide use in agriculture is easier by integration of traditional monitoring approaches and new computational tools

Introduction: Variable climatic and working conditions in open field, use of complex mixtures of agrochemicals and high cost make traditional approaches of occupational hygiene hardly feasible in small and medium agricultural enterprises. This calls for alternative strategies allowing risk assessment without/with minimal field measurement. This can be achieved through the use of predictive models in combination with environmental and biological monitoring measurements to build physically based \u2018exposure and risk profiles\u2019 to which specific, experimentally determined values of relevant parameters need to be assigned to finally derive specific exposure scenaria for the individual crops. Methods: To test feasibility of this approach, we pooled environmental and biological monitoring data collected in a pilot study of rice and maize herbicide applicators in Lombardy region, Italy. Exposure calculation based on monitoring data showed most workers are below the Acceptable Operator Exposure Level defined in the authorization process. Moreover, we set up a prototype method to calculate a provisional biological exposure limit to perform individual risk assessment based on biological monitoring in 24-hr urine. Results: The study estimated propanil median levels of workers\u2019 whole-body over-clothing exposure as 0.032 (0.01-1.24) parts-per-million.Farmers who used an open tractor did not show a significantly higher exposure than those who used closed or air-conditioned tractor cockpit. Measurements above and below clothing show \u2dc60% barrier efficiency of working clothes. Twenty-four-hour post-application, urine excretion of 3,4-dichloroaniline was \u2dc0.3 parts-per-million of applied propanil which is toxicologically irrelevant based on AOEL of 20 microg/kgbw/day. Discussion: We identified the main variables affecting exposure intensity in each of the main work phases of pesticide application. To each variable score were assigned ranking from excellent protection from excess exposure to risky condition leading to unacceptable exposure. Presumptive exposure levels and the corresponding protection factors were calculated and were in agreement with those calculated from real-life exposure measurements

Serum levels of polychlorinated biphenyls (PCBs) and organochorinated pesticides (OCPs) among individuals of general population in three Italian geographic regions

Purpose Despite extensive use of organochlorinated pesticides (OCPs) such as DDT in Italy in the 40\u2019s to 60\u2019s to control malaria vectors and of polychlorinated biphenyls (PCBs) in industry and energy production, limited information is available on current exposure among the general population of Italy. This study aims at measuring levels of some OCPs and PCBs in subjects of three different towns (Novafeltria, Pavia and Milano) with the final objective of relating exposure to these endocrine-disrupting agents to the occurrence of diseases such as breast cancer. Methods Blood samples were collected from 370 consenting subjects (163 in Novafeltria, 166 in Pavia, 41 in Milano). 36 PCBs and 8 OCPs were measured in blood serum by gas-chromatography-mass spectrometry. Statistical analysis aimed at highlighting differences in POPs levels with respects to residence, age, gender and body mass index. Results PCBs 138, 153 and 180 were the most frequently detected. Levels of total PCBs (in picomoles/g of circulating lipids) and dioxin-like PCBs were significantly different among the study sites (Novafeltriamales; p<0.0001). In the subjects from Novafeltria and Pavia, total PCBs and some abundant congeners showed a strong positive correlation with age, which points at life-long accumulation. Among OCPs, p,p\u2019-DDE and HCB were the most abundant. A significant difference in HCB, p, p\u2019-DDE and p,p\u2019-DDD levels was observed among the residents from the study sites. Females in Milan have significantly higher mean concentration than males (p=0.0491)