BACKGROUND:Per- and poly-fluoroalkyl substances (PFAS) are persistent and widespread environmental pollutants. People living in Veneto Region (Italy) have been exposed from the late 1970s to 2013 to elevated concentrations of PFAS through drinking water. The effect of PFAS on thyroid function is still controversial and studies focusing on thyroid stimulating hormone (TSH) have shown inconsistent results. The aim of this study was to evaluate the association between serum PFAS and TSH levels and its dose-response relationship in a large population of highly exposed individuals.METHODS:A cross-sectional study was conducted on 21,424 individuals aged 14-39 living in the contaminated area. In the main analysis, participants with prevalent thyroid disease and pregnant women were excluded. Serum levels of perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorohexanesulfonic acid (PFHxS) and perfluorononanoic acid (PFNA) were measured. Generalized Additive Models were used to evaluate the association between TSH levels and serum PFAS, using thin plate spline smooth terms to model the potential non-linear relationship. Models were stratified by sex and age group and adjusted for potential confounders. A secondary analysis was conducted to evaluate the association between PFAS with prevalent self-reported thyroid disorders.RESULTS:We found no association between TSH and any type of PFAS among adolescents or women. A decrease in TSH concentration was observed in association with an IQR increase in PFHxS and a mild decrease in TSH at low levels of PFOA, PFOS and PFHxS among male adults. Self-reported thyroid disease was more common among women with higher levels of PFNA concentrations, whereas all other PFAS were not associated with thyroid diseases regardless of sex or age.CONCLUSIONS:Overall there is no evidence of an association between TSH and PFAS. However, some results are suggestive of a possible inverse association of TSH with PFOA, PFOS and PFHxS among adult males.

Abstract Background Cities are health promoters, although many of them lack of spaces for sport practice. In the meanwhile, for instance, several recreational and sport spaces, that can be open to the community, are offered by the network of churches. A research is developing a tool for making more efficient the assets of sport activities in parishes in a multi-generational, inclusive and health education perspective, in response to increasingly evident needs related to social and sports demand, education health, enhancement of the built heritage and social inclusion. The social and technical value based tool merges several issues related to Public Health, Urban Health, sport facilities design, urbanism and social impact. Methods The first part of the tool refers to an urban analysis of the city to be investigated and it highlights the correlations among the parishes, sport infrastructures, population density and social inequalities, physical activity and green areas. All the analysis refer to the GIS systems in which all the data are collected and organized by districts. Results The application was done in the city of Milan (Italy). The analysis with GIS system gives rise to several maps (a-population health status with a focus on physical activity, b-sport infrastructures availability, c-parishes available, etc.) with different results and they have been merged together. Some areas show some critical aspects related to the lack of public sport spaces, green areas and social inequalities. It permits to select the case studies to be taken in consideration for the application of the Strategic Design Framework, and it will allow to give rise to a detailed examination of the parishes' potentialities for improving the sport practice. Conclusions The tool is working progress and it will be validated through the application on 5 case studies in the city of Milan. The research is funded by Politecnico di Milano - PoliSocial Award 2019, entitled “SPèS” (Sport is Society). Key messages Social governance, health promotion and urban inclusion, through the reactivation system of the sport infrastructures in the parishes of Milan. Local parishes as health promoters of sport practice: sport infrastructures for the local communities in Milan.

Background: Studies on the association between perfluoroalkyl substances (PFAS) and metabolic syndrome (MetS) are limited, and results are inconsistent. We aimed to examine the associations between PFAS serum levels and the prevalence of MetS among highly exposed young adults (ages 20–39) residents of a large area of the Veneto Region (North-Eastern Italy) primarily stemming from PFAS water contamination before September 2013. A total of 15,876 eligible young adult residents living in the investigated municipalities were enrolled in the study from January 2017 to July 2019. Methods: MetS was defined by using a modified harmonized definition requiring the presence of 3 of the following: obesity (body mass index ≥30), elevated triglyceride (TG), reduced high-density lipoprotein cholesterol, elevated blood pressure, and hemoglobin A1c ≥ 6.1% or self-reported diabetes mellitus or drug treatment for hyperglycemia. Multivariable generalized additive models were performed to identify the associations between four serum PFAS, including perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA), and risk of MetS controlling for potential confounders. Results: A total of 1282 participants (8.1%) met the criteria of MetS with a higher prevalence among men. PFOA, PFHxS, and PFNA were not associated with the risk of MetS, whereas PFOS showed a consistent protective effect against the risk of MetS (OR 0.76, (95% CI: 0.69, 0.85) per ln-PFOS). However, we found statistically significant positive associations between PFAS serum levels and individual components of MetS, mainly elevated blood pressure and elevated TG. Conclusion: Our results did not support a consistent association between PFAS and MetS and conflicting findings were observed for individual components of MetS.

Background and goals: A wide area in the Veneto region (northern Italy) has been faced a perfluoroalkyl substances (PFAS) contamination occurred mainly in groundwater and drinking water. Exposure of the population likely started in the Sixties, had a sure decrease after filters installation in 2013. The Veneto Region is conducting a biomonitoring study to investigate health conditions of the exposed population, collecting hundreds of serum samples. Some Physiologically based Pharmacokinetic (PBPK) models are being tested comparing PFOA and PFOS measured levels with the estimated ones.Methods: Original Loccisano model corrected by EFSA Scientific Panel was tested for this case study. A worst case scenario (WCS) and a best case scenario (BCS) were developed. Both scenarios took into account individual simulations carried out on 25 people (11 men and 14 women), aged 22-39 years, living in an area with both groundwater and drinking water contamination. WCS considered water intake from the private well, company water and bottled water in the same proportion. In the BCS we assumed 1/3 of the water intake from drinking water and 2/3 from bottled water.Results: Estimated average PFOA serum level obtained from the WCS was very near to the measured one for men (E:151.4±68.4;M:108.6±51.0 ng/mL), while was farther but still quite near the measured value for women (E:132.2±108.2;M:30.9±30.1 ng/mL). In the BCS the result is the opposite (men, E:23.9±10.4; women, E:22.1±13.2 ng/mL).Conclusions: Model seems to predict well PFOA serum levels in the exposed population even with high entity of uncertainties. Loccisano model is a multi-compartment PBPK model created specifically for PFAS, but with no modelization of menstruation and pregnancy losses. New simulations are being running to increase statistical significance but we are also looking at other models to take into account gender differences, to explain differences between men and women observed in measured data.

BACKGROUND: In spring 2013, groundwater of a vast area of the Veneto Region (northeastern Italy) was found to be contaminated by perfluoroalkyl substances (PFAS) from a PFAS manufacturing plant active since the late 1960s. Residents were exposed to high concentrations of PFAS, particularly perfluorooctanoic acid (PFOA), through drinking water until autumn 2013. A publicly funded health surveillance program is under way to aid in the prevention, early diagnosis, and treatment of chronic disorders possibly associated with PFAS exposure. OBJECTIVES: The objectives of this paper are: a) to describe the organization of the health surveillance program, b) to report serum PFAS concentrations in adolescents and young adults, and c) to identify predictors of serum PFAS concentrations in the studied population. METHODS: The health surveillance program offered to residents of municipalities supplied by contaminated waterworks includes a structured interview, routine blood and urine tests, and measurement of 12 PFAS in serum by high-performance liquid chromatography-tandem mass spectrometry. We studied 18,345 participants born between 1978 and 2002, 14-39 years of age at recruitment. Multivariable linear regression was used to identify sociodemographic, lifestyle, dietary, and reproductive predictors of serum PFAS concentrations. RESULTS: The PFAS with the highest serum concentrations were PFOA [median 44.4 ng/mL, interquartile range (IQR) 19.3-84.9], perfluorohexane-sulfonic acid (PFHxS) (median 3.9 ng/mL, IQR 1.9-7.4), and perfluorooctanesulfonic acid (PFOS) (median 3.9 ng/mL, IQR 2.6-5.8). The major predictors of serum levels were gender, municipality, duration of residence in the affected area, and number of deliveries. Overall, the regression models explained 37%, 23%, and 43% of the variance of PFOA, PFOS, and PFHxS, respectively. CONCLUSIONS: Serum PFOA concentrations were high relative to concentrations in populations with background residential exposures only. Interindividual variation of serum PFAS levels was partially explained by the considered predictors.

Background: Perfluoroalkyl substances (PFASs) are persistent and widespread environmental pollutants. People living in the North-East of Italy have been exposed from the late 1970s to 2013 to high concentrations of PFASs through drinking water. The role PFASs could play on thyroid function is still controversial and studies that focused on thyrotropin (TSH) showed inconsistent results. The aim of this study was to evaluate the association between serum PFASs and TSH levels and its dose-response shape in a large exposed population. Methods: A cross-sectional study was conducted in 14,993 individuals aged 20-39 living in the contaminated area. In the main analysis, patients with thyroid pathologies and pregnant women were excluded. Serum levels of perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorohexanesulfonic acid (PFHxS) and perfluorononanoic acid (PFNA) were measured by HPLC-MS/MS. Generalized Additive Models were used to evaluate the association between TSH levels and serum PFASs, using thin plate spline smooth terms to model the potential non-linear relationship. Models were stratified by gender and adjusted for potential confounders. A secondary analysis was conducted to evaluate the association between PFASs and the prevalence of self-reported thyroid disorders. Results: In both males and females, a statistically significant non-linear association was found with PFOS. The shape of the slopes shows a decrease in TSH concentration at low levels of PFOS but an increase at higher serum PFOS. PFOA in females was instead found to have a modest linear positive association with TSH. No association was found between TSH and PFNA or PFHxs. We also found higher odds of reporting thyroid disease with increased measured PFNA concentrations in women. Conclusions: Serum PFASs concentrations were modestly associated with thyroid function in this highly exposed young adults population suggesting this substance to be a possible endocrine disruptor. There is evidence of a non-linear association with TSH for PFOS.

Abstract Background Residents in a large area of North-Eastern Italy were exposed to perfluoroalkyl substances (PFAS) via drinking water. Studies on the association between PFAS and blood pressure levels are limited, and results are inconsistent. Using cross-sectional data from the Regional health surveillance program, we aimed to quantify the associations between PFAS serum concentrations and blood pressure and hypertension prevalence. Methods The study comprised 16,224 individuals aged 20–39 years. Pregnant women (n = 327), or individuals with missing information on the selected covariates (n = 111) were excluded, leaving 15,786 subjects for the analyses. Hypertension was defined as any self-reported diagnosis, use of antihypertensive drugs, or elevated systolic blood pressure (SBP ≥ 140 mmHg)/diastolic blood pressure (DBP ≥ 90 mmHg). Generalized additive models were used to investigate the relation between perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA)) natural log (ln) transformed and by decile, and SBP, DBP, hypertension, adjusted for potential confounders. Results Both SBP and DBP increased significantly with an increase in the ln-transformed serum PFAS concentrations in a monotonic way. The predicted increase in SBP and DBP were 1.54 mmHg (95%CI 0.61–2.47), 1.60 mmHg (95%CI 0.92–2.27) from lowest to highest decile of PFOA. The associations were stronger for SBP in men and for DBP in women. One unit increase in each In-transformed PFAS was positively associated with an increased odd of hypertension in men: PFOA OR = 1.06 (1.01–1.11), PFOS OR = 1.13 (1.03–1.23), PFHxS OR = 1.08 (1.02–1.15), PFNA OR = 1.20 (1.02–1.40). Conclusions Our findings suggest that serum PFAS concentrations were associated with increased systolic and diastolic blood pressure in a large highly exposed young adult population. Although the magnitude of the observed effect was relatively small, if confirmed it would be of public health relevance since even small increases in blood pressure levels at the population level may be associated to a raised risk of adverse outcomes such as cardiovascular disease and target organ damage.

PFASs (perfluoroalkyl and polyfluoroalkyl substances) are highly fluorinated, aliphatic, synthetic compounds with high thermal and chemical stability as well as unique amphiphilic properties which make them ingredients in a range of industrial processes. PFASs have attracted consideration due to their persistence, toxicity and bioaccumulation tendency in the environment. Recently, attention has begun to be addressed to shorter-chain PFASs, such as perfluorohexane sulfonate [PFHxS], apparently less toxic to and more easily eliminated from lab animals. However, short-chain PFASs represent end-products from the transformation of fluorotelomers whose biotic breakdown reactions have not been identified to date. This means that such emergent pollutants will tend to accumulate and persist in ecosystems. Since we are just learning about the interaction between short-chain PFASs and microorganisms, this study reports on the response to PFHxS of two Pseudomonas sp. strains isolated from environmental matrices contaminated by PFASs. The PFHxS bioaccumulation potential of these strains was unveiled by exploiting different physiological conditions as either axenic or mixed cultures under alkanothrofic settings. Moreover, electron microscopy revealed nonorthodox features of the bacterial cells, as a consequence of the stress caused by both organic solvents and PFHxS in the culturing substrate.

Background: Residents of a large area of North-Eastern Italy were exposed for decades to high concentrations of perfluoroalkyl and polyfluoroalkyl substances (PFAS) via drinking water. Serum PFAS levels have been consistently associated with elevated serum lipids, but few studies have been conducted among pregnant women, and none has stratified analyses by trimester of gestation. Elevated serum lipid levels during pregnancy can have both immediate and long-lasting effects on pregnant women and the developing fetus. We evaluated the association between perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), and perfluoro-hexanesulfonate (PFHxS) levels in relation to lipid profiles in highly-exposed pregnant women. Methods: A cross-sectional analysis was conducted in 319 pregnant women (age 14-48 years) enrolled in the Regional health surveillance program. Non-fasting blood samples were obtained in any trimester of pregnancy and analyzed for PFOA, PFOS and PFHxS, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C). Low-density lipoprotein cholesterol (LDL-C) was calculated. The associations between ln-transformed PFAS (and categorized into quartiles) and lipids were assessed using generalized additive models. Analyses were adjusted for potential confounders and stratified according to pregnancy trimester. Results: The geometric means of PFOA, PFOS and PFHxS were 14.78 ng/mL, 2.67 ng/mL and 1.89 ng/mL, respectively. The plasma levels of TC, HDL-C and LDL-C increased steadily throughout the trimesters. In the 1st trimester, PFOS was positively associated with TC and PFHxS with HDL-C. In the 3rd trimester, instead, an inverse relationship was seen between PFOA and PFHxS and both TC and LDL-C. Conclusions: Results suggest the associations between PFAS concentrations and lipid profiles in pregnant women might differ by trimesters of pregnancy. In the first trimester, patterns are similar to those of non-pregnant women, while they differ late in pregnancy. Different independent behavior of PFAS and lipid levels throughout the pregnancy might explain our observations. These findings support the ubiquitous exposure to PFAS and possible influence on lipid metabolisms during pregnancy and suggest a careful evaluation of the timing of PFAS measurement, when examining effects of PFAS during pregnancy on gestational outcomes related to serum lipids amounts.

Abstract Background Residents in a large area of the Veneto Region (North-Eastern Italy) were exposed to perfluoroalkyl substances (PFASs) via drinking water. Studies on the association between PFASs and blood pressure (BP) levels are limited and results are inconsistent. Using cross-sectional data from the Regional health surveillance program, we aimed to quantify the associations between PFAS serum concentrations and blood pressure and hypertension prevalence. Methods The study included 16,224 individuals aged 20-39 years. Pregnant women (n = 327), participants with self-reported diagnosis or under treatment (n = 296) or with missing information on the selected covariates (n = 114) were excluded, leaving 15,487 subjects. Hypertension (HYP) was defined as any self-reported diagnosis, use of antihypertensive drugs, or raised systolic/diastolic blood pressure (SBP)≥140, DBP ≥90 mmHg). Serum PFASs were measured by HPLC-MS. Generalized additive models were used to investigate the relation between each PFAS (perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA)) ln transformed and by decile, and SBP, DBP, HYP, adjusted for potential confounders. Results Both SBP and DBP increased significantly with an increase in the ln-transformed serum PFASs concentration in a monotonic way. The predicted increase in SBP and DBP were 1.62 (95% CI = 0.69, 2.55), 1.64 mmHg (95% CI = 0.96, 2.31) from lowest to highest decile of PFOA. The associations were stronger for SBP in men and DBP in women. One unit increase in each ln-PFAS was positively associated with an increased odds of HYP in men: PFOA OR = 1.07 (1.01-1.14), PFOS OR = 1.18 (1.05-1.32), PFHxS OR = 1.11 (1.03-1.19), PFNA OR = 1.19 (1.01-1.41). Conclusions Our findings suggest that exposure to PFAS is associated with increased blood pressure and thus may contribute as a risk factor for the development of cardiovascular diseases. Key messages Serum PFASs were associated with raised systolic blood pressure in men and diastolic blood pressure in women in a large highly exposed young adult population. Serum PFASs were associated with raised prevalence of hypertension in men.