{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:48:18Z","timestamp":1792792098015,"version":"4.5.0"},"reference-count":84,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2015,6,1]],"date-time":"2015-06-01T00:00:00Z","timestamp":1433116800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"},{"start":{"date-parts":[[2015,4,28]],"date-time":"2015-04-28T00:00:00Z","timestamp":1430179200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["setac.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>\u2003<\/jats:title>\n                    <jats:p>A need exists to better understand the influence of pH on the uptake and accumulation of ionizable pharmaceuticals in fish. In the present study, fathead minnows were exposed to diphenhydramine (DPH; disassociation constant\u2009=\u20099.1) in water for up to 96\u2009h at 3 nominal pH levels: 6.7, 7.7, and 8.7. In each case, an apparent steady state was reached by 24\u2009h, allowing for direct determination of the bioconcentration factor (BCF), blood\u2013water partitioning (PBW,TOT), and apparent volume of distribution (approximated from the whole-body\u2013plasma concentration ratio). The BCFs and measured PBW,TOT values increased in a nonlinear manner with pH, whereas the volume of distribution remained constant, averaging 3.0 L\/kg. The data were then simulated using a model that accounts for acidification of the gill surface caused by elimination of metabolically produced acid. Good agreement between model simulations and measured data was obtained for all tests by assuming that plasma binding of ionized DPH is 16% that of the neutral form. A simpler model, which ignores elimination of metabolically produced acid, performed less well. These findings suggest that pH effects on accumulation of ionizable compounds in fish are best described using a model that accounts for acidification of the gill surface. Moreover, measured plasma binding and volume of distribution data for humans, determined during drug development, may have considerable value for predicting chemical binding behavior in fish. Environ Toxicol Chem 2015;34:1425\u20131435. \u00a9 2015 SETAC<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/etc.2948","type":"journal-article","created":{"date-parts":[[2015,4,28]],"date-time":"2015-04-28T16:50:33Z","timestamp":1430239833000},"page":"1425-1435","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":107,"title":["Observed and modeled effects of pH on bioconcentration of diphenhydramine, a weakly basic pharmaceutical, in fathead minnows"],"prefix":"10.1093","volume":"34","author":[{"given":"John W.","family":"Nichols","sequence":"first","affiliation":[{"name":"Office of Research and Development, National Health and Environmental Effects Research LaboratoryMid-Continent Ecology Division, US Environmental Protection Agency Duluth Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bowen","family":"Du\u200c","sequence":"additional","affiliation":[{"name":"The Institute of Ecological, Earth and Environmental SciencesBaylor University Waco Texas USA"},{"name":"Center for Reservoir and Aquatic Systems ResearchBaylor University Waco Texas USA"},{"name":"Department of Environmental ScienceBaylor University Waco Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason P.","family":"Berninger\u200c","sequence":"additional","affiliation":[{"name":"Institute of Biomedical StudiesBaylor University Waco Texas USA"},{"name":"Center for Reservoir and Aquatic Systems ResearchBaylor University Waco Texas USA"},{"name":"Department of Environmental ScienceBaylor University Waco Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin A.","family":"Connors","sequence":"additional","affiliation":[{"name":"Institute of Biomedical StudiesBaylor University Waco Texas USA"},{"name":"Center for Reservoir and Aquatic Systems ResearchBaylor University Waco Texas USA"},{"name":"Department of Environmental ScienceBaylor University Waco Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.Kevin","family":"Chambliss\u200c","sequence":"additional","affiliation":[{"name":"Department of Chemistry and BiochemistryBaylor University Waco Texas USA"},{"name":"The Institute of Ecological, Earth and Environmental SciencesBaylor University Waco Texas USA"},{"name":"Center for Reservoir and Aquatic Systems ResearchBaylor University Waco Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell J.","family":"Erickson","sequence":"additional","affiliation":[{"name":"Office of Research and Development, National Health and Environmental Effects Research LaboratoryMid-Continent Ecology Division, US Environmental Protection Agency Duluth Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex D.","family":"Hoffman","sequence":"additional","affiliation":[{"name":"Office of Research and Development, National Health and Environmental Effects Research LaboratoryMid-Continent Ecology Division, US Environmental Protection Agency Duluth Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan W.","family":"Brooks","sequence":"additional","affiliation":[{"name":"Institute of Biomedical StudiesBaylor University Waco Texas USA"},{"name":"The Institute of Ecological, Earth and Environmental SciencesBaylor University Waco Texas USA"},{"name":"Center for Reservoir and Aquatic Systems ResearchBaylor University Waco Texas USA"},{"name":"Department of Environmental ScienceBaylor University Waco Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,6,1]]},"reference":[{"key":"2025010316034846200_etc2948-bib-0001","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1002\/qsar.200390023","article-title":"A generic QSAR for assessing the bioaccumulation potential of organic chemicals in aquatic food webs","volume":"22","author":"Arnot","year":"2003","journal-title":"QSAR Comb Sci"},{"key":"2025010316034846200_etc2948-bib-0002","doi-asserted-by":"crossref","first-page":"2343","DOI":"10.1897\/03-438","article-title":"A food web bioaccumulation model for organic chemicals in aquatic ecosystems","volume":"23","author":"Arnot","year":"2004","journal-title":"Environ Toxicol Chem"},{"key":"2025010316034846200_etc2948-bib-0003","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1080\/10659360500474623","article-title":"Base-line model for identifying the bioaccumulation potential of chemicals","volume":"16","author":"Dimitrov","year":"2005","journal-title":"SAR QSAR Environ Res"},{"key":"2025010316034846200_etc2948-bib-0004","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1007\/s11367-010-0165-6","article-title":"An unexpected challenge: Ionizable compounds in the REACH chemical space","volume":"15","author":"Franco","year":"2010","journal-title":"Int J Life Cycle Assess"},{"key":"2025010316034846200_etc2948-bib-0005","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/0045-6535(94)90040-X","article-title":"Surfactant bioconcentration: A critical review","volume":"29","author":"Tolls","year":"1994","journal-title":"Chemosphere"},{"key":"2025010316034846200_etc2948-bib-0006","doi-asserted-by":"crossref","first-page":"1554","DOI":"10.1021\/es0620484","article-title":"Spatial distribution of perfluoroalkyl contaminants in lake trout from the Great Lakes","volume":"41","author":"Furdui","year":"2007","journal-title":"Environ Sci Technol"},{"key":"2025010316034846200_etc2948-bib-0007","doi-asserted-by":"crossref","first-page":"2427","DOI":"10.1021\/es204164b","article-title":"Human therapeutic plasma levels of the selective serotonin reuptake inhibitor (SSRI) sertraline decrease serotonin reuptake transporter binding and shelter-seeking behavior in adult male fathead minnows","volume":"46","author":"Valenti","year":"2012","journal-title":"Environ Sci Technol"},{"key":"2025010316034846200_etc2948-bib-0008","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1289\/ehp.1104477","article-title":"Pharmaceuticals and personal care products in the environment: What are the big questions?","volume":"120","author":"Boxall","year":"2012","journal-title":"Environ Health Perspect"},{"key":"2025010316034846200_etc2948-bib-0009","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/0043-1354(94)00189-E","article-title":"Relation between toxicity and accumulation of chlorophenols at various pH, and their absorption mechanism in fish","volume":"29","author":"Kishino","year":"1995","journal-title":"Water Res"},{"key":"2025010316034846200_etc2948-bib-0010","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.1897\/08-233.1","article-title":"Methods for estimating the bioconcentration factor of ionizable organic chemicals","volume":"28","author":"Fu","year":"2009","journal-title":"Environ Toxicol Chem"},{"key":"2025010316034846200_etc2948-bib-0011","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1002\/etc.5620180412","article-title":"Improved method for estimating bioconcentration factor from octanol\/water partition coefficient","volume":"18","author":"Meylan","year":"1999","journal-title":"Environ Toxicol Chem"},{"key":"2025010316034846200_etc2948-bib-0012","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1080\/714044797","article-title":"A theoretical model for utilizing mammalian pharmacology and safety data to prioritize potential impacts of human pharmaceuticals to fish","volume":"9","author":"Huggett","year":"2003","journal-title":"Human Ecol Risk Assess"},{"key":"2025010316034846200_etc2948-bib-0013","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/S0166-445X(01)00174-6","article-title":"Branchial elimination of superhydrophobic organic compounds by rainbow trout (Oncorhynchus mykiss)","volume":"55","author":"Fitzsimmons","year":"2001","journal-title":"Aquat Toxicol"},{"key":"2025010316034846200_etc2948-bib-0014","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1002\/etc.590","article-title":"Effects of the antihistamine diphenhydramine on selected aquatic organisms","volume":"30","author":"Berninger","year":"2011","journal-title":"Environ Toxicol Chem"},{"key":"2025010316034846200_etc2948-bib-0015","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1002\/etc.2020","article-title":"Development and evaluation of a mechanistic bioconcentration model for ionogenic organic chemicals in fish","volume":"32","author":"Armitage","year":"2013","journal-title":"Environ Toxicol Chem"},{"key":"2025010316034846200_etc2948-bib-0016","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1897\/05-358R.1","article-title":"Uptake and elimination of ionizable organic chemicals at fish gills: I. Model formulation, parameterization, and behavior","volume":"25","author":"Erickson","year":"2006","journal-title":"Environ Toxicol Chem"},{"key":"2025010316034846200_etc2948-bib-0017","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1897\/05-359R.1","article-title":"Uptake and elimination of ionizable organic chemicals at fish gills: II. Observed and predicted effects of pH, alkalinity, and chemical properties","volume":"25","author":"Erickson","year":"2006","journal-title":"Environ Toxicol Chem"},{"key":"2025010316034846200_etc2948-bib-0018","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1002\/jps.3030450508","article-title":"Physical properties and pharmacological activity: Anthihistamines","volume":"45","author":"Lordi","year":"1956","journal-title":"J Am Pharm Assoc"},{"key":"2025010316034846200_etc2948-bib-0019","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.chroma.2003.11.007","article-title":"Determination of ionization constants of organic bases in aqueous methanol solutions using capillary electrophoresis","volume":"1026","author":"Buckenmaier","year":"2004","journal-title":"J Chromatogr A"},{"key":"2025010316034846200_etc2948-bib-0020","first-page":"2581","article-title":"Measurement of dissociation constants (pKa values) of organic compounds by multiplexed capillary electrophoresis using aqueous and cosolvent buffers","volume":"97","author":"Shaleva","year":"2008","journal-title":"J Pharm Sci"},{"key":"2025010316034846200_etc2948-bib-0021","volume-title":"Exploring QSAR. Hydrophobic, Electronic, and Steric Constants","author":"Hansch","year":"1995"},{"key":"2025010316034846200_etc2948-bib-0022","doi-asserted-by":"crossref","first-page":"1810","DOI":"10.1002\/etc.2240","article-title":"Comparative pharmaceutical metabolism by rainbow trout (Oncorhynchus mykiss) liver S9 fractions","volume":"32","author":"Connors","year":"2013","journal-title":"Environ Toxicol Chem"},{"key":"2025010316034846200_etc2948-bib-0023","doi-asserted-by":"crossref","first-page":"3155","DOI":"10.1021\/ac062215i","article-title":"Analysis of pharmaceuticals in fish using liquid chromatography-tandem mass spectrometry","volume":"79","author":"Ramirez","year":"2007","journal-title":"Anal Chem"},{"key":"2025010316034846200_etc2948-bib-0024","doi-asserted-by":"crossref","first-page":"2587","DOI":"10.1897\/08-561.1","article-title":"Occurrence of pharmaceuticals and personal care products in fish: Results of a national pilot study in the United States","volume":"28","author":"Ramirez","year":"2009","journal-title":"Environ Toxicol Chem"},{"key":"2025010316034846200_etc2948-bib-0025","doi-asserted-by":"crossref","first-page":"6073","DOI":"10.1021\/es8001162","article-title":"Application of solid-phase microextraction for in vivo laboratory and field sampling of pharmaceuticals in fish","volume":"42","author":"Zhou","year":"2008","journal-title":"Environ Sci Technol"},{"key":"2025010316034846200_etc2948-bib-0026","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.chroma.2012.07.026","article-title":"Evaluation of an isotope dilution liquid chromatography tandem mass spectrometry method for pharmaceuticals in fish","volume":"1253","author":"Du","year":"2012","journal-title":"J Chromatogr A"},{"key":"2025010316034846200_etc2948-bib-0027","doi-asserted-by":"crossref","first-page":"20140058","DOI":"10.1098\/rstb.2014.0058","article-title":"Bioaccumulation and trophic dilution of human pharmaceuticals across trophic levels of an effluent-dependent wadeable stream","volume":"369","author":"Du","year":"2014","journal-title":"Phil Trans R Soc B"},{"key":"2025010316034846200_etc2948-bib-0028","author":"US Environmental Protection Agency.","year":"2002","edition":"5th ed"},{"key":"2025010316034846200_etc2948-bib-0029","author":"American Public Health Association.","year":"1995","edition":"19th ed"},{"key":"2025010316034846200_etc2948-bib-0030","author":"US Environmental Protection Agency.","year":"1991","edition":"2nd ed"},{"key":"2025010316034846200_etc2948-bib-0031","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1002\/jps.2600690614","article-title":"Effects of different buffer species on partition coefficients of drugs used in quantitative structure-activity relationships","volume":"69","author":"Wang","year":"1980","journal-title":"J Pharm Sci"},{"key":"2025010316034846200_etc2948-bib-0032","author":"Virtual Computational Chemistry Laboratory.","year":"2011"},{"key":"2025010316034846200_etc2948-bib-0033","author":"Royal Society of Chemistry.","year":"2015"},{"key":"2025010316034846200_etc2948-bib-0034","author":"ChemAxon."},{"key":"2025010316034846200_etc2948-bib-0035","author":"Organisation for Economic Co-operation and Development.","year":"2006"},{"key":"2025010316034846200_etc2948-bib-0036","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1002\/etc.5620220512","article-title":"Slow-stirring method for determining the n-octanol\/water partition coefficient (Pow) for highly hydrophobic chemicals: Performance evaluation in a ring test","volume":"22","author":"Tolls","year":"2003","journal-title":"Environ Toxicol Chem"},{"key":"2025010316034846200_etc2948-bib-0037","doi-asserted-by":"crossref","first-page":"2661","DOI":"10.1021\/es903440m","article-title":"Therapeutic levels of levonorgestrel detected in blood plasma of fish: Results from screening rainbow trout exposed to treated sewage effluents","volume":"44","author":"Fick","year":"2010","journal-title":"Environ Sci Technol"},{"key":"2025010316034846200_etc2948-bib-0038","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1016\/j.scitotenv.2013.07.126","article-title":"Comparison of contaminants of emerging concern removal, discharge and water quality hazards among centralized and on-site wastewater treatment systems receiving common wastewater influent","volume":"466\u2013467","author":"Du","year":"2014","journal-title":"Sci Total Environ"},{"key":"2025010316034846200_etc2948-bib-0039","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/S0141-1136(00)00048-9","article-title":"Pathology of fathead minnows (Pimephales promelas) exposed to chlorine dioxide and chlorite","volume":"50","author":"Yonkos","year":"2000","journal-title":"Mar Environ Res"},{"key":"2025010316034846200_etc2948-bib-0040","author":"Yonkos","year":"2000"},{"key":"2025010316034846200_etc2948-bib-0041","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0166-445X(97)00018-0","article-title":"An ultrastructural examination of the mode of UV-induced toxic action of fluoranthene in the fathead minnow, Pimephales promelas","volume":"39","author":"Weinstein","year":"1997","journal-title":"Aquat Toxicol"},{"key":"2025010316034846200_etc2948-bib-0042","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/0300-9629(79)90070-7","article-title":"Oxygen consumption in the fathead minnow (Pimephales promelas Rafinesque). I. Effects of weight, temperature, group size, oxygen level and opercular movement rate as a function of temperature","volume":"62C","author":"Wares","year":"1979","journal-title":"Comp Biochem Physiol"},{"key":"2025010316034846200_etc2948-bib-0043","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1242\/jeb.126.1.41","article-title":"Acid-based regulation and ion transfers in the carp (Cyprinus carpio): pH compensation during graded long- and short-term environmental hypercapnia, and the effect of bicarbonate infusion","volume":"126","author":"Claiborne","year":"1986","journal-title":"J Exp Biol"},{"key":"2025010316034846200_etc2948-bib-0044","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1242\/jeb.137.1.457","article-title":"Effect of adrenaline and blood gas conditions on red cell volume and intra-erythrocytic electrolytes in the carp, Cyprinus carpio","volume":"137","author":"Fuchs","year":"1988","journal-title":"J Exp Biol"},{"key":"2025010316034846200_etc2948-bib-0045","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1007\/BF00003402","article-title":"Interrelationships between red cell nucleoside triphosphate content, and blood pH, O2-tension and haemoglobin concentration in the carp, Cyprinus carpio","volume":"8","author":"Jensen","year":"1990","journal-title":"Fish Physiol Biochem"},{"key":"2025010316034846200_etc2948-bib-0046","first-page":"769","article-title":"Effects of hypoxia on renal function in carp","volume":"101A","author":"Kakuta","year":"1992","journal-title":"Comp Biochem Physiol"},{"key":"2025010316034846200_etc2948-bib-0047","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1023\/A:1007856808003","article-title":"Intracellular pH regulation of rainbow trout and carp thrombocytes","volume":"21","author":"Nikinmaa","year":"1999","journal-title":"Fish Physiol Biochem"},{"key":"2025010316034846200_etc2948-bib-0048","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/0166-445X(90)90001-6","article-title":"A model for exchange of organic chemicals at fish gills: Flow and diffusion limitations","volume":"18","author":"Erickson","year":"1990","journal-title":"Aquat Toxicol"},{"key":"2025010316034846200_etc2948-bib-0049","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1897\/1551-5028(1998)017<1447:EOLKOA>2.3.CO;2","article-title":"Evaluation of log KOW and tissue lipid content as predictors of chemical partitioning to fish tissues","volume":"17","author":"Bertelsen","year":"1998","journal-title":"Environ Toxicol Chem"},{"key":"2025010316034846200_etc2948-bib-0050","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1002\/aic.690010222","article-title":"Correlation of diffusion coefficients in dilute solutions","volume":"1","author":"Wilke","year":"1955","journal-title":"Am Inst Chem Eng J"},{"key":"2025010316034846200_etc2948-bib-0051","author":"Organisation for Economic Co-operation and Development.","year":"1996"},{"key":"2025010316034846200_etc2948-bib-0052","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.1002\/etc.2238","article-title":"Uptake and depuration of pharmaceuticals in reclaimed water by mosquito fish (Gambusia holbrooki): A worst-case, multiple-exposure scenario","volume":"32","author":"Wang","year":"2013","journal-title":"Environ Toxicol Chem"},{"key":"2025010316034846200_etc2948-bib-0053","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1177\/1177391X0700100003","article-title":"The pKa distribution of drugs: Application to drug discovery","volume":"1","author":"Manallack","year":"2007","journal-title":"Perspect Medicin Chem"},{"key":"2025010316034846200_etc2948-bib-0054","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1007\/BF01060888","article-title":"Effects of pH on the accumulation of sulfonamides by fish","volume":"9","author":"Lo","year":"1981","journal-title":"J Pharmacokinet Biopharm"},{"key":"2025010316034846200_etc2948-bib-0055","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/0147-6513(82)90032-X","article-title":"Relation between physicochemical properties of phenols and their toxicity and accumulation in fish","volume":"6","author":"Saarikoski","year":"1982","journal-title":"Ecotoxicol Environ Saf"},{"key":"2025010316034846200_etc2948-bib-0056","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/0147-6513(86)90060-6","article-title":"Factors affecting the absorption of phenolics and carboxylic acids in the guppy (Poecilia reticulata)","volume":"11","author":"Saarikoski","year":"1986","journal-title":"Ecotoxicol Environ Safety"},{"key":"2025010316034846200_etc2948-bib-0057","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1016\/j.chemosphere.2007.06.089","article-title":"The effects of pH on fluoxetine in Japanese medaka (Orysias latipes): Acute toxicity in fish larvae and bioaccumulation in juvenile fish","volume":"70","author":"Nakamura","year":"2008","journal-title":"Chemosphere"},{"key":"2025010316034846200_etc2948-bib-0058","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1007\/BF01067905","article-title":"Pharmacokinetics of diphenhydramine in humans","volume":"3","author":"Albert","year":"1975","journal-title":"J Pharmacokinet Biopharm"},{"key":"2025010316034846200_etc2948-bib-0059","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1038\/clpt.1980.155","article-title":"Diphenhydramine in Orientals and Caucasians","volume":"28","author":"Spector","year":"1980","journal-title":"Clin Pharmacol Ther"},{"key":"2025010316034846200_etc2948-bib-0060","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1002\/etc.2219","article-title":"Towards improved models for predicting the bioconcentration of well-metabolized compounds by rainbow trout using measured rates of in vitro intrinsic clearance","volume":"32","author":"Nichols","year":"2013","journal-title":"Environ Toxicol Chem"},{"key":"2025010316034846200_etc2948-bib-0061","doi-asserted-by":"crossref","first-page":"2293","DOI":"10.1021\/tx200431b","article-title":"Serum albumin binding of structurally diverse neutral organic compounds: Data and models","volume":"24","author":"Endo","year":"2011","journal-title":"Chem Res Toxicol"},{"key":"2025010316034846200_etc2948-bib-0062","doi-asserted-by":"crossref","first-page":"12697","DOI":"10.1021\/es303379y","article-title":"Partitioning of neutral organic compounds to structural proteins","volume":"46","author":"Endo","year":"2012","journal-title":"Environ Sci Technol"},{"key":"2025010316034846200_etc2948-bib-0063","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1897\/07-016R.1","article-title":"The sorptive capacity of animal protein","volume":"26","author":"de Bruyn","year":"2007","journal-title":"Environ Toxicol Chem"},{"key":"2025010316034846200_etc2948-bib-0064","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.aca.2013.04.030","article-title":"Elucidating the sorption mechanism of \u201cmixed mode\u201d SPME using the basic drug amphetamine as a model compound","volume":"782","author":"Peltenburg","year":"2013","journal-title":"Anal Chim Acta"},{"key":"2025010316034846200_etc2948-bib-0065","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1002\/jez.10125","article-title":"Acid-base regulation in fishes: Cellular and molecular mechanisms","volume":"293","author":"Claiborne","year":"2002","journal-title":"J Exp Zool"},{"key":"2025010316034846200_etc2948-bib-0066","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1152\/physrev.00050.2003","article-title":"The multifunctional fish gill: Dominant site of gas exchange, osmoregulation, acid-base regulation, and excretion of nitrogenous waste","volume":"85","author":"Evans","year":"2005","journal-title":"Physiol Rev"},{"key":"2025010316034846200_etc2948-bib-0067","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.resp.2006.04.010","article-title":"Acid-base balance and CO2 excretion in fish: Unanswered questions and emerging models","volume":"154","author":"Perry","year":"2006","journal-title":"Respir Physiol Neurobiol"},{"key":"2025010316034846200_etc2948-bib-0068","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1242\/jeb.029181","article-title":"Carbonic anhydrase and acid-base regulation in fish","volume":"212","author":"Gilmour","year":"2009","journal-title":"J Exp Biol"},{"key":"2025010316034846200_etc2948-bib-0069","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1242\/jeb.149.1.149","article-title":"The effect of varying water pH on the acidification of expired water in rainbow trout","volume":"149","author":"Lin","year":"1990","journal-title":"J Exp Biol"},{"key":"2025010316034846200_etc2948-bib-0070","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1007\/BF00694377","article-title":"Water chemistry changes in the gill micro-environment of rainbow trout: Experimental observations and theory","volume":"159B","author":"Playle","year":"1989","journal-title":"J Comp Physiol"},{"key":"2025010316034846200_etc2948-bib-0071","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1242\/jeb.126.1.499","article-title":"Downstream pH changes in water flowing over the gills of rainbow trout","volume":"126","author":"Wright","year":"1986","journal-title":"J Exp Biol"},{"key":"2025010316034846200_etc2948-bib-0072","doi-asserted-by":"crossref","first-page":"2401","DOI":"10.1029\/98WR01530","article-title":"Data from selected US Geological Survey national stream water quality monitoring networks","volume":"34","author":"Alexander","year":"1998","journal-title":"Water Resources Res"},{"key":"2025010316034846200_etc2948-bib-0073","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.aquatox.2006.01.017","article-title":"In vitro-in vivo extrapolation of hepatic metabolism data for fish: I. A review of methods and strategy for incorporating intrinsic clearance estimates into chemical kinetic models","volume":"78","author":"Nichols","year":"2006","journal-title":"Aquat Toxicol"},{"key":"2025010316034846200_etc2948-bib-0074","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/S0378-4274(02)00045-0","article-title":"Pharmacodynamic activity of drugs and ecotoxicology: Can the two be connected?","volume":"131","author":"Seiler","year":"2002","journal-title":"Toxicol Lett"},{"key":"2025010316034846200_etc2948-bib-0075","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/S0378-4274(03)00066-3","article-title":"Aquatic ecotoxicology of fluoxetine","volume":"142","author":"Brooks","year":"2003","journal-title":"Toxicol Lett"},{"key":"2025010316034846200_etc2948-bib-0076","doi-asserted-by":"crossref","first-page":"8211","DOI":"10.1021\/es072658j","article-title":"Repeating history: Pharmaceuticals in the environment","volume":"41","author":"Ankley","year":"2007","journal-title":"Environ Sci Technol"},{"key":"2025010316034846200_etc2948-bib-0077","first-page":"97","volume-title":"Effects of Veterinary Medicines in the Environment","author":"Brooks","year":"2008"},{"key":"2025010316034846200_etc2948-bib-0078","doi-asserted-by":"crossref","first-page":"8965","DOI":"10.1021\/es801611a","article-title":"Herbicidal effects of sulfamethoxazole in Lemna gibba: Using p-aminobenzoic acid as a biomarker of effect","volume":"42","author":"Brain","year":"2008","journal-title":"Environ Sci Technol"},{"key":"2025010316034846200_etc2948-bib-0079","doi-asserted-by":"crossref","first-page":"5807","DOI":"10.1021\/es8005173","article-title":"Evolutionary conservation of human drug targets in organisms used for environmental risk assessments","volume":"42","author":"Gunnarsson","year":"2008","journal-title":"Environ Sci Technol"},{"key":"2025010316034846200_etc2948-bib-0080","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.toxlet.2009.12.006","article-title":"Leveraging mammalian pharmaceutical toxicology and pharmacology data to predict chronic fish responses to pharmaceuticals","volume":"193","author":"Berninger","year":"2010","journal-title":"Toxicol Lett"},{"key":"2025010316034846200_etc2948-bib-0081","doi-asserted-by":"crossref","first-page":"11384","DOI":"10.1021\/es402065a","article-title":"The read-across hypothesis and environmental risk assessment of pharmaceuticals","volume":"47","author":"Rand-Weaver","year":"2013","journal-title":"Environ Sci Technol"},{"key":"2025010316034846200_etc2948-bib-0082","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1289\/ehp.1306638","article-title":"Current perspectives on the use of alternative species in human health and ecological hazard assessments","volume":"121","author":"Perkins","year":"2013","journal-title":"Environ Health Perspect"},{"key":"2025010316034846200_etc2948-bib-0083","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1111\/j.1365-2125.2008.03351.x","article-title":"A pharmacokinetic evaluation of five H1 antagonists after an oral and intravenous microdose to human subjects","volume":"67","author":"Madan","year":"2009","journal-title":"Br J Clin Pharmacol"},{"key":"2025010316034846200_etc2948-bib-0084","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.aquatox.2014.01.007","article-title":"Fish on Prozac (and Zoloft): Ten years later","volume":"151","author":"Brooks","year":"2014","journal-title":"Aquat Toxicol"}],"container-title":["Environmental Toxicology and Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fetc.2948","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fetc.2948","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/etc\/article-pdf\/34\/6\/1425\/60106831\/etc2948.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/etc\/article-pdf\/34\/6\/1425\/60106831\/etc2948.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T12:48:53Z","timestamp":1748350133000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/etc\/article\/34\/6\/1425\/7761813"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,6,1]]},"references-count":84,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2015,6,1]]},"published-print":{"date-parts":[[2015,6,1]]}},"URL":"https:\/\/doi.org\/10.1002\/etc.2948","relation":{},"ISSN":["0730-7268","1552-8618"],"issn-type":[{"value":"0730-7268","type":"print"},{"value":"1552-8618","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2015,6,1]]},"published":{"date-parts":[[2015,6,1]]},"assertion":[{"value":"2014-10-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-02-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-04-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}