Assessing the longitudinal trend of POP concentrations in humans using high-throughput sample preparation methods developed for low-volume samples

Abstract: Human exposure to anthropogenic persistent organic pollutants (POPs) and their related effects on human health widely vary from person to person, making population-based risk assessment difficult.This thesis aimed to evaluate how individual changes and implemented re-strictions in POP production influenced human exposure. High-throughput sample preparation methods were developed and applied to plasma samples col-lected for an epidemiological study so that the longitudinal change in concen-trations of a broad range of chlorinated (Cl), brominated (Br) and fluorinated POPs in humans could be efficiently evaluated.Two 96-well plate extraction methods were used to determine the concentra-tions of Cl/Br POPs and fluorinated POPs in 150μL of plasma samples collected for the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Plasma samples from 1,016 men and women were collected three times between 2001 and 2014, after participants turned 70, 75 and 80 years old. Dif-ferences in longitudinal trends were observed between Cl/Br POPs and fluori-nated POPs as a result of their differences in time of production and imple-mented restrictions in use. The five year trend in 17 Cl POPs (14 polychlorinated biphenyls and 3 organochlorine pesticides), detected in the majority of the co-hort, and a tetra-brominated diphenyl ether detected in 34% of the follow-up samples showed a significant decrease in plasma concentrations. However, the change in Cl/Br POP concentrations was found to be slower in those who lost more weight and had greater increases in plasma lipids, and showed a faster decline in men versus women. The 8 perfluoroalkyl substances (PFASs) detected in the majority of the cohort showed an overall increase in PFHxS, PFNA, PFDA, and PFUnDA, while PFHpA, PFOA, FOSA, and L-PFOS showed a de-crease over ten years. One of the PFASs that showed an overall increasing trend was heavily influenced by the percentage of PFAS-contaminated drinking water distributed to the residential area.The developed and applied methods showed a high-throughput with precise and consistent results using small sample amounts and the longitudinal trend of POPs in a prospective cohort was efficiently produced. Important information was gained on how residential location, physiological differences and changes, and implemented restrictions in POP production has effected human trends.