Behavior-Based Thresholds Support Screening-Level Prioritization of Caffeine as a Neuroactive Wastewater Micropollutant in Coastal Waters.

Sensitive functional end points reveal early responses to neuroactive wastewater contaminants but are rarely translated into screening thresholds. Using caffeine as a sentinel, we evaluated a behavior-based framework for coastal waters. Systematic searches of Web of Science Core Collection, PubMed, and Embase through 24 August 2026 identified 66 eligible studies and 2181 effect sizes for meta-analysis. The near-zero grand pooled signed ln RR may reflect cancellation among end points with opposing response directions. Responses varied by life stage, exposure duration, concentration, and end point category. Standardized light-dark assays across eight aquatic species revealed taxon- and context-dependent behavioral disruptions, including responses at low concentration and non-monotonic patterns. Species sensitivity distributions based on behavioral benchmark concentrations yielded a conservative hazardous concentration affecting 5% of species (HC5; 0.0585 μg L-1) and a screening-level behavior-based predicted no-effect concentration (PNEC; 0.0195 μg L-1). A separate systematic literature search, supplemented with NORMAN EMPODAT records, compiled 1421 quantifiable caffeine measurements in coastal and estuarine waters. Concentrations were right-skewed (median, 44.9 ng L-1; IQR, 14.60-190.00 ng L-1), and 69.88% of measurements fell into the high-priority risk quotient category (RQ ≥ 1). These findings support behavior-based thresholds for prioritizing neuroactive wastewater pollution in coastal waters.