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We tested a human to fish biological read-across hypothesis for contaminant disposition by examining tissue-specific accumulation in three understudied species, longnose gar (Lepisosteus osseus; piscivore), gizzard shad (Dorosoma cepedianum; planktivore\/detritivore), and smallmouth buffalo (Ictiobus bubalus; benthivore), from a river influenced by municipal effluent discharge. In addition to surface water, fish plasma, and brain, gill, gonad, liver, and lateral muscle fillet tissues were analyzed via isotope dilution liquid chromatography tandem mass spectrometry. Caffeine and sucralose, two common effluent tracers, were quantitated at low micrograms per liter levels in surface water, while an anticonvulsant, carbamazepine, was observed at levels up to 37\u2009ng\/L. The selective serotonin reuptake inhibitors (SSRIs) fluoxetine and sertraline and primary metabolites were detected in at least one tissue of all three species at low micrograms per kilogram concentrations. Within each species, brain and liver of select fish contained the highest levels of SSRIs compared to plasma and other tissues, which is generally consistent with human tissue disposition patterns. However, we observed differential accumulation among specific tissue types and species. For example, mean levels of sertraline in brain and liver tissues were 13.4\u2009\u00b5g\/kg and 1.5\u2009\u00b5g\/kg in gizzard shad and 1.3\u2009\u00b5g\/kg and 7.3\u2009\u00b5g\/kg in longnose gar, respectively. In contrast, smallmouth buffalo did not consistently accumulate SSRIs to detectable levels. Tissue-specific eco-exposome efforts are necessary to understand mechanisms associated with such marked bioaccumulation and internal dispositional differences among freshwater fish species occupying different trophic positions. Environ Toxicol Chem 2024;43:1894\u20131902. \u00a9 2024 The Author(s). Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.<\/jats:p>","DOI":"10.1002\/etc.5931","type":"journal-article","created":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T12:14:34Z","timestamp":1718712874000},"page":"1894-1902","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The Tissue-Specific Eco-Exposome: Differential Pharmaceutical Bioaccumulation and Disposition in Fish among Trophic Positions"],"prefix":"10.1093","volume":"43","author":[{"given":"Jaylen L.","family":"Sims","sequence":"first","affiliation":[{"name":"Department of Environmental Science Baylor University Waco Texas USA"},{"name":"Center for Reservoir and Aquatic Systems Research Baylor University Waco Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander R.","family":"Cole","sequence":"additional","affiliation":[{"name":"Department of Environmental Science Baylor 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