Reclaimed water irrigation in hydroponics: Dose–dependent uptake of PMT substances and implications for lettuce and human health

Hydroponic agriculture combined with reclaimed water use represents a sustainable strategy to address global water scarcity. However, the presence of persistent, mobile, and toxic (PMT) substances in reclaimed water raises emerging concerns for environmental safety and food security. This study examines the impact of five concentration levels (0.05-500 μg L^-1) of a nine-compound PMT mixture, including venlafaxine, O-desmethyl venlafaxine, ofloxacin, terbutryn, 1H-benzotriazole, (4 + 5)-methylbenzotriazole, galaxolidone, perfluorobutanesulfonic acid (PFBS), and perfluoropentanoic acid (PFPeA), on hydroponically cultivated lettuce under controlled greenhouse conditions. A multidisciplinary assessment was conducted, including contaminant uptake and bioaccumulation, agronomic performance, plant metabolomics, in-vitro toxicological bioassays, and a theoretical human health risk assessment. Results showed compound-specific accumulation, with PFPeA and galaxolidone reaching 559 and 483 ng g^-1 fresh weight, respectively. Agronomic effects ranged from hormetic responses at environmentally relevant low concentrations to phototoxic stress at higher exposures. Although no effects were detected in toxicological bioassays, PFPeA exceeded risk thresholds (HQ = 1-25) at concentrations ≥50 μg L^-1, indicating potential concern for human exposure via vegetable crop consumption. These findings underscore the need for environmentally realistic dose-response studies to inform regulatory thresholds and ensure the safe use of reclaimed water in food production systems.