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.