Stage-resolved attenuation of pharmaceutical mixture risk in a full-scale lagoon-wetland wastewater treatment system

Wastewater treatment performance is commonly evaluated based on contaminant removal, although environmental protection ultimately depends on reducing the cumulative ecological risk imposed by complex pharmaceutical mixtures. Here, we investigated the barrier-specific attenuation of estrogens, antidepressants, and antiretrovirals in a full-scale lagoon treatment system coupled to a pilot-scale constructed wetland by integrating repeated-measures ANOVA, barrier-specific log removal values (LRV), deterministic ecological risk assessment, and probabilistic mixture modeling using species sensitivity distributions (SSDs), and multisubstance potentially affected fraction (msPAF). Mean influent concentrations were 31.07 μg L⁻¹ for lamivudine and 322.75, 119.52, and 33.73 ng L⁻¹ for estrone, 17β-estradiol, and estriol, respectively. Pharmaceutical attenuation differed markedly among treatment barriers, with limited removal under anaerobic conditions and substantially greater attenuation during oxidative treatment and tertiary polishing. The constructed wetland provided the greatest incremental ecological protection, accounting for approximately 91.4% of the total cumulative deterministic ecological risk attenuation. Deterministic ecological risk identified efavirenz as the dominant contributor to cumulative long-term ecological risk, accounting for approximately 99.9% of the cumulative long-term deterministic risk throughout the wastewater treatment train. The short-term probabilistic mixture risk declined progressively from 0.651 in the influent to 0.602 after secondary treatment and was modeled as zero following tertiary wetland polishing. These findings demonstrate that wastewater treatment performance is more appropriately evaluated through barrier-specific ecological risk attenuation than concentration removal alone and highlight nature-based tertiary treatment as a highly effective strategy for mitigating pharmaceutical risks before environmental discharge.