0ABSTRACT Title of thesis: EXAMINATION OF THE ASSOCIATIONS BETWEEN SELECTED PERFLUOROALKYL SUBSTANCES AND THEIR ISOMERS WITH BODY WEIGHT IN ADOLESCENTS USING NHANES 2013-2018 Jessica Snyder, Master of Science, 2023 Thesis Directed by: Professor Devon Payne-Sturges Maryland Institute for Applied Environmental Health Perfluoroalkyl substances (PFAS), a class of environmentally persistent chemicals, are suspected of having obesogenic properties, with studies thus far being inconclusive. Few past studies of PFAS toxicity have distinguished between isomer types of each PFAS group during analysis, however. In this thesis, data for non-smoking 14-19 year-olds from three cycles of the National Health and Nutrition Examination Survey was analyzed to identify potential associations in adolescents between bodyweight and two major families of PFAS: perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) and to additionally determine if differentiating between linear and branched isomeric groups of two major PFAS families could better elucidate any associations found. In unadjusted models, weighted linear regression of body mass index (BMI) and serum concentrations of branched, linear, and total PFAS isomer groups, all returned positive associations ranging from β (95% confidence interval) of 4.06 (3.44, 4.68) for total PFOS to 12.33 (10.39,14.28) for linear PFOA. When models were adjusted for sex, age, race/ethnic origin and income level, however, only a negative association between BMI and branched PFOS (bPFOS) was found, with β= -1.24 (-2.10, -0.39). Unadjusted weighted logistic regression models of both overweight and obese status resulted in positive associations between obesity and both branched PFOS and total PFOS with odds ratios (95% confidence intervals) of 0.45 (0.27, 0.74) and 0.86 (0.75, 0.99) respectively. After adjusting for potential confounders, the only statistically significant relationship was between branched bPFOS and obesity, with a 56% decrease in the odds of obesity for every unit increase in serum concentration of bPFOS [β =-1.06, adjusted odds ratio= 0.44 (0.26,0.76)]. There was no significant difference between the sexes in any results. The apparent protective effect that bPFOS has against obesity and elevated BMI, notable as a health outcome association in itself, also illustrates that isomeric differentiation is important in studying PFAS, as nPFOS had no statistically significant 1 association by itself while ΣPFOS, used by many studies, did. Thus, the lack of differentiation could mask which PFAS type contributes to any associations discovered.