Biochemical and haematological effects of serum PFOA, ADV and cC6O4 in workers of a chemical company producing fluoropolymers, Italy, 2013–2022

ntroduction: Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are widely used in the manufacture of fluo- ropolymers. We evaluated biochemical and haematological effects of three PFAS, serum perfluorooctanoic acid (PFOA), ADV, and cC6O4 in workers of a fluoropolymer company. Methods: Using data (2013–2022), we fitted random intercept regression models adjusted for several covariates and reciprocal adjustment between the three PFAS. Results: We analysed data of 814 workers (698 men, 116 women), 607 from the chemical plant, 207 from the research centre, for a total of 4912 blood samples (2065 with all three PFAS measured). Median levels of PFOA and ADV were 21.3 and 120 μg/L. Most (65.5%) cC6O4 measurements were below the limits of quantification (which varied over time from 5 to 0.1 μg/L). For PFOA, we observed positive associations with total cholesterol (+1.1% increase per ln(PFOA) increase) and apolipoprotein B (+1.4%) and negative associations with alkaline phosphatase ( 1.5%); suggestive associations were also found with RBC ( 0.4%), IgA ( 1.5%), IgM ( 1.4%). ADV was positively associated with total and LDL cholesterol (+1.0% and +1.6% per ln(ADV) increase), apolipoprotein B (+1.0%), GGT (+2.1%), IgM (+1.4%), and WBC (+1.5%) and negatively associated with direct bilirubin ( 2.3%) and alpha-2-globulins ( 0.7%); suggestive associations were found for indirect bilirubin ( 2.0%), oestradiol ( 2.1%), ad CRP (+6.0%). For samples with detectable cC6O4 levels we observed higher values of ALP (+2.3%), proteins (+0.5%), IgG (+0.7%) and platelets (+1.6%) and suggestively increased total bilirubin (+3.9%), RBC (+0.6%), and oestradiol (+5.8%). Some associations (total cholesterol, apolipoprotein B, WBC, total bilirubin, and alkaline phosphatase showed reverse time trends in parallel with the strong decrease of serum PFOA and ADV over the study period. Discussion: We found associations of serum PFOA and ADV with lipid metabolism, liver function, and immu- noglobulins. The reverse time trends of some endpoints in parallel with decrease of serum PFOA and ADV reinforce causal interpretation of results. cC6O4 showed a different pattern of associations.