Pharmaceuticals have been most commonly used as medicine to treat human and animal diseases, and as animal feed supplements to promote growth. These applications have rendered the ubiquitous presence of pharmaceuticals in animal excretions and their discharges from wastewater treatment plants (WWTPs). Land application of animal manures and biosolids from WWTPs and crop irrigation with reclaimed water result in the dissemination of these pharmaceuticals in agricultural soils and waters. Crops and vegetables could take up pharmaceuticals from soil and water, leading to the accumulation of trace-level pharmaceuticals in fresh produce. The pharmaceutical concentrations in crops and vegetables are much lower than the dosage for effective therapy. However, the impacts of long-term consumption of pharmaceutical-tainted crops/vegetables to human and animal health remain nearly unknown. Currently, the mechanism of plant uptake of pharmaceuticals from soil and water is not clear, which impedes the development of effective measures to mitigate contamination of food crops by pharmaceuticals. We hypothesize that water flow is the primary carrier for pharmaceuticals to enter plants, and plant physiological characteristics, pharmaceutical physicochemical properties as well as plant-pharmaceutical interactions (e.g., sorption affinity) collectively influence pharmaceutical accumulation and transport in plants. In this work, a sensitive and effective extraction method was first developed to quantify the uptake of thirteen pharmaceuticals by lettuce (Lactuca sativa) from water. The results indicated that small-sized pharmaceuticals with molecular weight (MW) < 300 g mol−1 could enter lettuce, and those pharmaceuticals with low affinity to lettuce roots such as caffeine and carbamazepine could substantially transport to shoots. A strong positive linear relation was observed between their mass accumulation in shoots and the amount of transpiration water. Lamotrigine and trimethoprim are also small-sized pharmaceuticals; however, their relatively strong affinity to lettuce roots mitigated the amount of transfer to shoots. Large-sized pharmaceuticals (MW > 400 g mol−1) such as lincomycin, monensin sodium, oxytetracycline and tylosin were primarily accumulated in lettuce roots with limited amount to transfer to shoots. The results of mass balance showed that acetaminophen, β-estradiol, carbadox, estrone, and triclosan were readily metabolized in lettuce with ≥ 90% loss during 144-h exposure period. A workflow for identification of non-targeted metabolites was developed using liquid chromatography coupled to hybrid triple quadrupole-linear ion trap mass spectrometer, and this method was applied to investigate the metabolism of caffeine in lettuce. The results revealed that caffeine underwent metabolism in lettuce with > 50% loss during 144-h exposure period. The major metabolism reaction was demethylation forming the products of losing one, two or three methyl functional groups, and these products accounted for 20% of the initial dosage of caffeine. Caffeine also underwent oxidation and hydroxylation reactions in lettuce. Overall, this study sheds new light to uptake pathways and transport characteristics of pharmaceuticals in vegetables (e.g. lettuce). The mechanistic insights obtained could help form a framework for exposure modelling of diverse pharmaceutical compounds, and facilitate the development of scientifically informed management strategies to mitigate pharmaceutical accumulation in agricultural food produce.
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