Temporal and geographic variability of bisphenol levels in humans: A systematic review and meta-analysis of international biomonitoring data

Introduction: Bisphenols are endocrine-disrupting chemicals known to contribute to chronic disease across the lifespan. With increased awareness of their health effects, changes in regulation and health behaviors have contributed to reductions in urinary bisphenol A (BPA) levels in the United States, Canada, and Europe. However, global trends in bisphenols outside these regions, especially bisphenol S (BPS) exposure, have been less studied. Aim: We examine trends in urinary BPA and BPS concentration in non-occupationally exposed populations, where representative data at a country level is unavailable. Methods: We systematically reviewed studies published between 2000 and 2023 that included urinary bisphenol concentrations. We examined BPA and BPS concentration changes by sampling year, controlling for region, age, and pregnancy status, with and without a quadratic term and geometric mean, via mixed-effects meta-regression models with a random intercept and sensitivity analysis. We identified heterogeneity using Cochran's Q-statistic, I2 index, and funnel plots. Results: The final analytic sample consisted of 164 studies. We observed positive non-linear associations between time and BPA concentration internationally (beta: 0.02 ng/mL/year2, 95% CI: [0.01, 0.03]) and in Eastern and Pacific Asia (beta: 0.03 ng/mL/year2, 95% CI: [0.02, 0.05]). We also observed non-linear associations of time with both BPA and BPS concentrations in the Middle East and South Asia (beta: 0.13 ng/mL/year2, 95% CI: [0.01, 0.25] and beta: 0.29 ng/mL/year2, 95% CI: [-0.50,-0.08], respectively). In the sensitivity analyses excluding studies with geometric or arithmetic mean values, each displayed significant shifts from the main findings with some consistent outcomes occurring internationally and/or in specific regions. Heterogeneity was high across studies, suggesting possible bias in our estimations. Conclusions: Our findings provide evidence for concern about increasing population exposure to BPA and BPS. Further studies estimating attributable disease burden and costs at regional and global levels are warranted to show these chemicals' impact on population health and economies.