A nationwide cross-sectional study led by the Agency for Toxic Substances and Disease Registry in collaboration with research and community partners, was designed to investigate health outcomes linked to per- and polyfluoroalkyl substances (PFAS) exposure among residents of communities with contaminated drinking water. The objective was to describe the study design, methods, participant demographics, and PFAS serum concentrations. From 2019 to 2023, adult (18+) and child (ages 4-17) participants were recruited from communities with past or ongoing PFAS contamination of drinking water across eight sites in California, Colorado, Massachusetts, Michigan, New Hampshire, New York, New Jersey, and Pennsylvania. Data on demographics, lifestyle factors, and residential, occupational, and medical history were collected via questionnaires. Extensive clinical tests assessed cardiometabolic, liver, thyroid, kidney, glycemic, and immune parameters. Neurobehavioral tests were administered to children (ages 5-17). PFAS quantified in serum included MeFOSAA, PFHxS, PFOS, PFOA, PFNA, PFDA, and PFUnDA. Serum, whole blood, and urine samples were banked for future analyses. The study enrolled 5826 adults (geometric mean age: 53.6 years; 60.2 % female; 77.2 % non-Hispanic White) and 710 children (geometric mean age: 10.7 years; 48.5 % female; 69 % non-Hispanic White). Compared with NHANES data (2017-2020), adults showed elevated geometric mean concentrations of PFHxS and PFOA; only PFHxS was elevated in children. These serum concentrations reflect a wide range of PFAS exposures in communities affected by contamination from firefighting activities and industrial emissions, and other sources. This large study is a valuable resource for exploring associations between PFAS exposure and health effects in adults and children.

Dioxins and dioxin-like compounds measurements were added to polychlorinated biphenyls (PCBs) and organochlorine pesticides to expand the exposure profile in a follow-up to the Anniston Community Health Survey (ACHS II, 2014) and to study diabetes associations. Participants of ACHS I (2005-2007) still living within the study area were eligible to participate in ACHS II. Diabetes status (type-2) was determined by a doctor's diagnosis, fasting glucose ≥1 mg/dL, or being on any glycemic control medication. Incident diabetes cases were identified in ACHS II among those who did not have diabetes in ACHS I, using the same criteria. Thirty-five ortho-substituted PCBs, 6 pesticides, 7 polychlorinated dibenzo-p-dioxins (PCDD), 10 furans (PCDF), and 3 non-ortho PCBs were measured in 338 ACHS II participants. Dioxin toxic equivalents (TEQs) were calculated for all dioxin-like compounds. Main analyses used logistic regression models to calculate odds ratios (OR) and 95 % confidence intervals (CI). In models adjusted for age, race, sex, BMI, total lipids, family history of diabetes, and taking lipid lowering medication, the highest ORs for diabetes were observed for PCDD TEQ: 3.61 (95 % CI: 1.04, 12.46), dichloro-diphenyl dichloroethylene (p,p'-DDE): 2.07 (95 % CI 1.08, 3.97), and trans-Nonachlor: 2.55 (95 % CI 0.93, 7.02). The OR for sum 35 PCBs was 1.22 (95 % CI: 0.58-2.57). To complement the main analyses, we used BKMR and g-computation models to evaluate 12 mixture components including 4 TEQs, 2 PCB subsets and 6 pesticides; suggestive positive associations for the joint effect of the mixture were found but were not significant. These results add support to earlier findings for diabetes associations with PCBs, PCDDs, trans-Nonachlor and p,p'- DDE.