Non-monotonic Association Between Chlorinated Polyfluorinated Ether Sulfonic Acids Exposure and the Risk of Overweight/Obesity Status in Adults

Chlorinated polyfluorinated ether sulfonic acids (Cl-PFESAs, including 6:2 Cl-PFESA and 8:2 Cl-PFESA), one of poly- and perfluoroalkyl substances (PFAS), used as perfluorooctane sulfonate (PFOS) alternatives in electroplating industry. Evidence in vivo and in vitro indicates that Cl-PFESAs might disrupt lipid metabolism. However, the association between Cl-PFESAs exposure and the prevalence of overweight/obesity in human is unknown. We conducted a cross-sectional study to investigate associations of serum 6:2 Cl-PFESA and 8:2 Cl-PFESA exposure with overweight/obesity status in adults. We quantified four perfluoroalkyl substances (PFAS), including 6:2 Cl-PFESA, 8:2 Cl-PFESA, PFOS, and perfluorooctanoic acid (PFOA) in 1275 Chinese adults from the Isomers of C8 Health Project in China study. Characteristics of participants were gathered from interviewer-administered questionnaires and anthropometric measurements. We classified overweight/obesity based on body mass index (BMI) according to WHO. Participants were categorized into normal weight group (BMI < 25 kg/m²) and overweight/obesity group (BMI ≥ 25 kg/m²). The detection proportion of 6:2 Cl-PFESA was 100% among the participants in this study. Adjusted for potential confounders, BMI in the second quartile of each ln-ng/mL greater concentration of 6:2 Cl-PFESA and 8:2 Cl-PFESA was 0.45 [95% confidence interval (CI): 0.08, 0.82], and 0.39 (95% CI:0.03, 0.76) significantly higher than the lowest quartile, respectively. Cl-PFESAs displayed inverted U-shaped associations with the risk of overweight/obesity, and the inflection point of 6:2 Cl-PFESA and 8:2 Cl-PFESA was 1.80 ng/mL, 0.01 ng/mL, respectively. For example, The risk of overweight/obesity increased (OR= 1.94; 95%CI: 1.24, 3.01) until around 1.80 ng/mL of predicted 6:2 Cl-PFESA concentration and then decreased (OR= 0.69; 95%CI: 0.39, 1.21). PFOS was associated with waist circumference (WC) but not BMI in each quartile. For PFOA, the associations with outcomes were linearly positive (P for trend < 0.05). This study reports the first observations on non-monotonic associations between serum 6:2 Cl-PFESA and 8:2 Cl-PFESA concentrations and the prevalence of overweight/obesity in adults. Our findings suggest that Cl-PFESAs may have endocrine disrupting characteristics, and this exposure-outcome association is a challenge for risk assessment of Cl-PFESAs. But more epidemiological investigations are required to confirm the observed associations.