Sitagliptin beyond low aquatic risk: mobility, transformation products, and mixture uncertainty in water-reuse...

Sitagliptin is commonly treated as a low-concern pharmaceutical in conventional aquatic risk assessment of the parent compound. That conclusion is useful, but it becomes incomplete when treated wastewater, biosolids, dissolved organic matter (DOM), co-occurring antidiabetic drugs, and transformation products (TPs) reshape exposure pathways. This focused critical narrative review uses sitagliptin as a model compound for testing the limits of predicted environmental concentration/predicted no-effect concentration (PEC/PNEC) framing in wastewater-impacted and water-reuse agroecosystems. The evidence base combines direct sitagliptin studies with mechanistic literature on pharmaceutical occurrence, soil sorption, reclaimed-water irrigation, crop uptake, mixture behavior, treatment transformation, hyporheic attenuation, and regulatory assessment. Direct soil evidence shows that sitagliptin retention is strongly matrix-dependent: sorption varies with soil organic matter and pH, whereas co-exposure to biosolids, sewage effluent, and metformin can reduce sorption under the tested conditions, plausibly increasing mobility. Field-scale reclaimed-water studies support soil exposure and accumulation, but they do not demonstrate edible-crop contamination or food-chain risk. Treatment and hyporheic studies further show that parent-compound attenuation often reflects transformation rather than complete risk closure, making TP identity, persistence, mobility, and toxicity central to interpretation. The review therefore does not reclassify sitagliptin as a proven high-risk contaminant. Instead, it identifies sitagliptin as a useful sentinel for a wider assessment problem: low aquatic parent-compound risk should not automatically close environmental evaluation when land application, DOM, mixtures, and TPs shape fate.