Three decades of mercury research in the Tapajós River Basin, Brazilian Amazon: Scientific progress, remaining uncertainties, and future challenges.

Over the past three decades, the Tapajós River Basin, Brazilian Amazon, has become a major setting for investigating chronic environmental mercury (Hg) exposure, predominantly associated with dietary methylmercury (MeHg) intake through fish consumption. This critical review synthesizes Hg research conducted between 1990 and 2026, tracing scientific progress from contamination sources to human exposure, health effects, biological susceptibility, and emerging environmental health challenges. Early studies identified artisanal and small-scale gold mining, the remobilization of legacy Hg through biogeochemical processes, and fish consumption as central components linking environmental Hg sources to human exposure. Subsequent investigations expanded this evidence by examining health effects, biological susceptibility, nutritional interactions, and multiple environmental stressors. Although Hg concentrations in piscivorous fish have remained persistently elevated, biomonitoring studies suggest a gradual decline in Hg exposure in some communities, potentially reflecting changes in dietary patterns, socioeconomic conditions, sampling characteristics, and study locations. Despite major advances in characterizing contamination and exposure, less progress has been achieved in understanding long-term health consequences. Most epidemiological studies remain descriptive or cross-sectional, limiting causal inference and characterization of exposure-response relationships. Neurological, sensory, visual, and motor alterations remain the most consistently reported outcomes, yet uncertainties persist regarding causality, individual susceptibility, and mechanisms underlying variability among exposed populations. The contrasting findings of the Faroe Islands and Seychelles longitudinal cohorts illustrate these challenges. Recent studies increasingly recognize that Hg toxicity is shaped by complex exposomes involving selenium (Se), co-exposure to lead (Pb) and other contaminants, nutritional transition, infectious diseases, climate change, and social determinants of health. Future progress will require adequately powered longitudinal cohorts, population-specific reference values, biomarkers of exposure, effect and susceptibility, and integration of multi-omics, exposome, and One Health approaches to strengthen causal inference and improve environmental health policies for Amazonian populations.