Effetti dei PFAS sulla salute nella comunità esposta a PFAS della Regione Veneto

Per- and polyfluoroalkyl substances (PFAS) are a class of synthetic chemicals widely used in industrial and consumer products since the 1940s, prized for their resistance to heat, water, and oil. However, these same properties make PFAS highly persistent in the environment, earning them the label "forever chemicals". As a result, PFAS are now ubiquitous, contaminating water, soil, and air worldwide, and exposing human populations primarily through contaminated drinking water, food, and household products. PFAS bioaccumulate in the body, raising serious concerns about long-term health risks. Scientific studies have linked PFAS exposure to various adverse health outcomes, including liver toxicity, immune suppression, endocrine disruption, developmental issues, and increased cancer risk. Despite the growing body of evidence, uncertainties remain regarding their mechanisms of action, variability in health effects, and the impacts of chronic low-dose exposure, making further research essential for advancing public health and regulatory policies. This dissertation aims to address critical gaps in understanding PFAS exposure and its health implications through three key objectives: examining the combined effects of PFAS mixtures, investigating longitudinal changes in serum PFAS levels, and analysing the excretion rates of these chemicals. These objectives are pursued using epidemiological data from the health surveillance program in the Veneto region, where residents have been exposed to PFAS-contaminated drinking water for decades. The first two studies applied mixture-based statistical models to assess the combined effects of multiple PFAS compounds on cardiometabolic outcomes in both occupationally exposed and highly exposed subjects. These analyses revealed significant adverse health effects of PFAS exposure, particularly concerning cholesterol levels, and were among the first to utilize novel statistical approaches in this context. By disentangling the individual contributions of each PFAS compound, these studies provided a more accurate assessment of the health risks posed by combined chemical exposures, highlighting the limitations of single-pollutant analyses. To explore the impact of longitudinal changes in PFAS exposure, the fourth study examined whether variations in serum PFAS levels are associated with changes in cholesterol levels over time. This study, representing one of the few longitudinal investigations on such topic, demonstrated significant associations suggesting that PFAS adverse health effect on cholesterol may be reversible. Its design minimized reverse causation and confounding, offering a clearer understanding of the dynamics of PFAS exposure and its health impacts. Additionally, the study explored the role of age, sex, and other potential effect modifiers, providing novel insights into how individual characteristics influence these associations. The final objective of this dissertation was reached with the third original contribution, aiming to estimate the half-life of PFOA in serum while identifying factors influencing its elimination. This study, the largest of its kind, provided precise half-life estimates in a population of young adults whose exposure via drinking water has largely ceased. It also highlighted the influence of lifestyle factors, such as alcohol consumption and smoking, on PFAS excretion rates, contributing to the understanding of the mechanisms driving PFAS elimination. By advancing the knowledge of PFAS mixtures, longitudinal exposure effects, and elimination rates, this research contributes to broader efforts to mitigate the health risks associated with PFAS exposure. The findings from this work offer important insights for future regulatory measures and public health policies aimed at protecting populations from PFAS-related harm.