B-382 Associations of Serum Per- and Polyfluoroalkyl Substances (PFAS) Levels with Clinical Indicators in a Clinical Patient Cohort

Abstract

Per- and polyfluoroalkyl substances (PFAS) are ubiquitous and persistent environmental contaminants. Extensive population-based biomonitoring has confirmed the widespread of PFAS in the general population. In 2022, National Academies of Sciences, Engineering, and Medicine (NASEM) issued clinical guidance recommending the measurement of nine specific serum PFAS analytes and A summed value =20 ng/mL is suggested as a threshold for additional clinical screening. Here we examined PFAS levels in clinical specimens and their relationship to clinical biomarkers that are associated with a variety of health conditions. We conducted a study using deidentified remnant serum specimens from an offline assessment. A validated LC-MS/MS method was used to quantify the nine NASEM-recommended PFAS analytes. A summed concentration of nine PFAS compounds was calculated, utilizing a 0.07 ng/mL value for PFAS analytes with levels below the assay-defined 0.1 ng/mL cutoff for all analytes. A retrospective review was conducted of available laboratory test results of clinical biomarkers from the remnant specimens in this study. Spearman correlation was performed between PFAS levels and recent clinical biomarker data, adjusted for patient’s gender and age. All statistical tests were two-sided, and p value<0.05 was considered statistically significant. A total 1,559 remnant specimens were included for PFAS testing with mean NASEM_SUM at 7.61 ng/mL and median at 5.22 ng/mL. Only 5 (0.3%) specimens showed all PFAS compounds at less than the 0.1 ng/mL cutoffs, while 1,554 (99.7%) had at least one positive PFAS. Compared to our published 2024 clinical assessment data and NHANES 2017-2020 studies, the positivity rates remained the same: >90% for linear PFOS, linear PFOA, PFHxS, branched PFOS, and PFNA; <50% for PFDA, PFUnDA, and MeFOSAA. PFAS levels were age- and gender-dependent: higher in older patients and males. Recent historical data of 13 biomarkers were retrieved from 1,380 individuals in prior remnant specimens. With age and gender adjusted, numerical correlation analysis showed significant (p<0.01) relationships between the PFAS NASEM_SUM and glucose, bilirubin, platelet count, LDL, non-HDL, and total cholesterol (TC). For individual PFAS compounds, significant numerical associations were observed within several groups: linear PFOS correlated with bilirubin, triglyceride (TG) and thyroid-stimulating hormone (TSH); branched PFOS correlated with bilirubin; and linear PFOA correlated with glucose, AST, non-HDL and total cholesterol (TC). Furthermore, PFHxS was associated with ALT, bilirubin and TC; PFNA showed significance with bilirubin, HDL, TC and TSH; PFDA correlated with glucose, TG and TC; PFUnDA showed relationships with glucose, TG and TC; and MeFOSAA correlated exclusively with HbA1c. With statistically significance observed, the magnitudes of the correlations were small with coefficients less than 0.2. This study is the first to apply the NASEM PFAS summation to study the relationship between PFAS and comprehensive clinical biomarkers. We identified significant but weak correlations across 12 biomarkers, and the PFAS effects weren't uniform and varied by compound. Our subsequent efforts will be directed toward expanding the cohort to enable more robust assessment of biomarker levels and the occurrence of the abnormal levels especially in the individuals with PFAS NASEM_SUM =20 ng/mL.