Association between 6:2 chlorinated polyfluoroalkyl ether sulfonic acid exposure and glucolipid metabolism in Chinese adults: a meta-analysis

Abstract Background In China, 6:2 chlorinated polyfluoroalkyl ether sulfonic acid (6:2 Cl-PFESA), commercially designated as F-53B, has been predominantly implemented as the perfluorooctane sulfonate (PFOS) substitute, with its 8:2 derivative showing negligible relevance to population exposure. Previous studies have found that 6:2 Cl-PFESA is closely related to dyslipidemia and disrupted glucose homeostasis, though results remain inconsistent. Methods Our study aimed to separately investigate the potential associations of 6:2 and 8:2 Cl-PFESA with glucolipid metabolism indicators in Chinese adults. A comprehensive systematic literature search was conducted across three major databases—PubMed, Embase, and Web of Science—by 23 September 2024. Random effects models were employed to estimate changes in blood lipid and glucose parameters with one interquartile range (IQR) increment in mean blood concentration of 6:2 and 8:2 Cl-PFESA. Subgroup analyses were performed based on different populations and types of diabetes. A Bayesian random-effects meta-regression model was conducted to attribute differences apparent between individual empirical estimates to mean 6:2 Cl-PFESA concentration. Results The analysis included 17 publications with more than 17, 000 participants. Meta-analyses revealed that each IQR increase of 6:2 Cl-PFESA exhibited significantly positive correlations with a 3.90 mg/dl change in total cholesterol (TC) (95% CI: 1.97, 5.83), and a 2.94 mg/dl change in low-density lipoprotein cholesterol (LDL-C) (95% CI: 1.47, 4.41) among the general adult population. The odds ratio (OR) for gestational diabetes mellitus (GDM) among pregnant women exposed to 6:2 Cl-PFESA was 1.61 (95% CI: 1.15, 2.27). Studies on 8:2 Cl-PFESA were insufficient. Conclusion The results demonstrated that 6:2 Cl-PFESA was significantly related to TC, LDL-C, as well as the risk of GDM. These findings challenge the current industrial designation of 6:2 Cl-PFESA as a safer alternative, necessitating explicit regulatory re-evaluation pending comprehensive mechanistic evidence that elucidates its biological interactions. Systematic review registration PROSPERO CRD42024581843