Exposure to second-generation flame retardants and risk of metabolic diseases: a systematic review and meta-analysis.

As replacements for legacy flame retardants, second-generation organophosphorus flame retardants (OPFRs) exhibit high environmental mobility and persistence, resulting in ubiquitous human exposure. The metabolic impacts of OPFR exposure remain controversial despite extensive epidemiological investigation. Comprehensive searches were performed in four databases up to Nov 2025. Following independent selection and quality grading by two reviewers, meta-analysis was conducted using R (version 4.4.3). Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using fixed- or random-effects models, depending on the I² statistic. The robustness of findings was verified via subgroup, sensitivity, and publication bias analyses, while restricted cubic spline regression characterized dose-response relationships. OPFR exposure was significantly associated with an elevated risk of metabolic diseases (OR = 1.11, 95% CI: 1.09–1.14, p < 0.0001). Stronger associations for chlorinated (OR = 1.36, 95% CI: 1.22–1.52) and aryl-OPFRs (OR = 1.39, 95% CI: 1.12–1.72). Significant positive associations in both Chinese (OR = 1.37, 95% CI: 1.19–1.57) and US populations (OR = 1.14, 95% CI: 1.07–1.21). Blood biomarkers yielded higher risk estimates (OR = 1.67, 95% CI: 1.62–2.26) than urine (OR = 1.25, 95% CI: 1.15–1.35). OPFRs were linked to diabetes (OR = 1.39, 95% CI: 1.16–1.68), obesity (OR = 1.35, 95% CI: 1.16–1.57), metabolic liver disease (OR = 1.56, 95% CI: 1.18–2.07), metabolic syndrome (OR = 1.58, 95% CI: 1.32–1.89), and dyslipidemia (OR = 1.18, 95% CI: 1.02–1.37). This study reveals a significant positive association between OPFR exposure and metabolic disease risk, with distinct dose-response patterns identified across various OPFR congeners. This highlights OPFRs as critical environmental risk factors and underscores the public health risks they pose.