Predicted and observed therapeutic dose exceedances of ionizable pharmaceuticals in fish plasma from urban coastal systems

Instream flows of the rapidly urbanizing watersheds and estuaries of the Gulf of Mexico in Texas (USA) are increasingly dominated by reclaimed waters. Though ionizable pharmaceuticals have received increasing attention in freshwaters, many research questions remain unanswered, particularly in tidally influenced urban coastal systems, which experience significant spatiotemporal variability in pH that influences bioavailability and bioaccumulation. The authors coupled fish plasma modeling of therapeutic hazard values with field monitoring of water chemistry variability and pharmaceutical occurrence to examine whether therapeutic hazards to fish existed within these urban coastal ecosystems and whether therapeutic hazards differed within and among coastal locations and seasons. Spatial and temporal fluctuations in pH within study sites altered the probability of encountering pharmaceutical hazards to fish. Significant water quality differences were consistently observed among traditional parameters and pharmaceuticals collected from surface and bottom waters, which are rarely sampled during routine surface water quality assessments. The authors then compared modeling predictions of fish plasma concentrations of pharmaceuticals to measured plasma levels from various field-collected fish species. Diphenhydramine and diltiazem were observed in plasma of multiple species, and diltiazem exceeded human therapeutic doses in largemouth bass, catfish, and mullet inhabiting these urban estuaries. Though the present study only examined a small number of target analytes, which represent a microcosm of the exposome of these fish, coastal systems are anticipated to be more strongly influenced by continued urbanization, altered instream flows, and population growth in the future. Unfortunately, aquatic toxicology information for diltiazem and many other pharmaceuticals is not available for marine and estuarine organisms, but such field observations suggest that potential adverse outcomes should be examined.

[1]  Erik Kristiansson,et al.  Evolutionary conservation of human drug targets in organisms used for environmental risk assessments. , 2008, Environmental science & technology.

[2]  Ruben Abagyan,et al.  In Silico Analysis of the Conservation of Human Toxicity and Endocrine Disruption Targets in Aquatic Species , 2014, Environmental science & technology.

[3]  P. Sutton,et al.  The coasts of our world: Ecological, economic and social importance , 2007 .

[4]  Bryan W Brooks,et al.  Leveraging mammalian pharmaceutical toxicology and pharmacology data to predict chronic fish responses to pharmaceuticals. , 2010, Toxicology letters.

[5]  R. Nicholls,et al.  A global analysis of human settlement in coastal zones , 2003 .

[6]  Richard Grace,et al.  Method validation and reconnaissance of pharmaceuticals, personal care products, and alkylphenols in surface waters, sediments, and mussels in an urban estuary. , 2013, Environment international.

[7]  M. Elliott,et al.  The Need for Definitions in Understanding Estuaries , 2002 .

[8]  R. Schwarzenbach,et al.  Evaluation of Liposome−Water Partitioning of Organic Acids and Bases. 1. Development of a Sorption Model , 2000 .

[9]  R. D. Doyle,et al.  Influence of Climate Change on Reservoir Water Quality Assessment and Management , 2011 .

[10]  S. Swearer,et al.  Fluctuations in natural and synthetic estrogen concentrations in a tidal estuary in south-eastern Australia. , 2013, Water research.

[11]  K. Bruland,et al.  Diel biogeochemical cycling in a hyperventilating shallow estuarine environment , 2000 .

[12]  D. Roelke,et al.  Anticipated human population and climate change effects on algal blooms of a toxic haptophyte in the south-central USA 1 , 2012 .

[13]  P. Montagna,et al.  The effect of freshwater inflow on meiofaunal and macrofaunal populations in the Guadalupe and Nueces Estuaries, Texas , 1992 .

[14]  E. Thurman,et al.  Pharmaceuticals, hormones, and other organic wastewater contaminants in U.S. streams, 1999-2000: a national reconnaissance. , 2002 .

[15]  Kristin A Connors,et al.  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. , 2012, Environmental science & technology.

[16]  Bryan W Brooks,et al.  Influence of drought and total phosphorus on diel pH in wadeable streams: Implications for ecological risk assessment of ionizable contaminants , 2011, Integrated environmental assessment and management.

[17]  B. Brooks.  Fish on Prozac (and Zoloft): ten years later. , 2014, Aquatic toxicology.

[18]  C. Chambliss,et al.  Bioaccumulation and trophic dilution of human pharmaceuticals across trophic positions of an effluent-dependent wadeable stream , 2014, Philosophical Transactions of the Royal Society B: Biological Sciences.

[19]  Mats Tysklind,et al.  Predicted critical environmental concentrations for 500 pharmaceuticals. , 2010, Regulatory toxicology and pharmacology : RTP.

[20]  K. Thomas,et al.  Sources, impacts and trends of pharmaceuticals in the marine and coastal environment , 2014, Philosophical Transactions of the Royal Society B: Biological Sciences.

[21]  J. Sekizawa,et al.  The effects of pH on fluoxetine in Japanese medaka (Oryzias latipes): acute toxicity in fish larvae and bioaccumulation in juvenile fish. , 2008, Chemosphere.

[22]  W. Cai,et al.  The chemistry, fluxes, and sources of carbon dioxide in the estuarine waters of the Satilla and Altamaha Rivers, Georgia , 1998 .

[23]  C. Chambliss,et al.  Aquatic toxicity of sertraline to Pimephales promelas at environmentally relevant surface water pH , 2009, Environmental toxicology and chemistry.

[24]  Kyungho Choi,et al.  Pharmaceuticals and Personal Care Products in the Environment: What Are the Big Questions? , 2012, Environmental health perspectives.

[25]  B. Cosby,et al.  Longitudinal and seasonal patterns of stream acidity in a headwater catchment on the Appalachian Plateau, West Virginia, U.S.A. , 1999 .

[26]  Mats Tysklind,et al.  Therapeutic levels of levonorgestrel detected in blood plasma of fish: results from screening rainbow trout exposed to treated sewage effluents. , 2010, Environmental science & technology.

[27]  Haiqing Li,et al.  Management of coastal mega-cities—a new challenge in the 21st century , 2003 .

[28]  R. Erickson,et al.  Observed and modeled effects of pH on bioconcentration of diphenhydramine, a weakly basic pharmaceutical, in fathead minnows , 2015, Environmental toxicology and chemistry.

[29]  S. Weisberg,et al.  CHARACTERIZING DISSOLVED OXYGEN CONDITIONS IN ESTUARINE ENVIRONMENTS , 1997 .

[30]  Bryan W Brooks,et al.  Bioaccumulation of human pharmaceuticals in fish across habitats of a tidally influenced urban bayou , 2016, Environmental toxicology and chemistry.

[31]  Paul A. Montagna,et al.  Effect of restored freshwater inflow on macrofauna and meiofauna in upper Rincon Bayou, Texas, USA , 2002 .

[32]  R. A. Snyder,et al.  Influence of an Oyster Reef on Development of the Microbial Heterotrophic Community of an Estuarine Biofilm , 2004, Applied and Environmental Microbiology.

[33]  D. Orvos,et al.  Aquatic toxicity of triclosan , 2002, Environmental toxicology and chemistry.

[34]  Richard A Brain,et al.  Herbicidal effects of sulfamethoxazole in Lemna gibba: using p-aminobenzoic acid as a biomarker of effect. , 2008, Environmental science & technology.

[35]  C. Chambliss,et al.  Effects of the antihistamine diphenhydramine on selected aquatic organisms , 2011, Environmental toxicology and chemistry.

[36]  Bryan W Brooks,et al.  Comparison of contaminants of emerging concern removal, discharge, and water quality hazards among centralized and on-site wastewater treatment system effluents receiving common wastewater influent. , 2014, The Science of the total environment.

[37]  S. Holm.  A Simple Sequentially Rejective Multiple Test Procedure , 1979 .

[38]  D. Barceló,et al.  Occurrence, distribution and partitioning of nonionic surfactants and pharmaceuticals in the urbanized Long Island Sound Estuary (NY). , 2014, Marine pollution bulletin.

[39]  Kristin A Connors,et al.  Comparative pharmaceutical metabolism by rainbow trout (Oncorhynchus mykiss) liver S9 fractions , 2013, Environmental toxicology and chemistry.

[40]  J. Sumpter,et al.  Quantitative Cross-Species Extrapolation between Humans and Fish: The Case of the Anti-Depressant Fluoxetine , 2014, PloS one.

[41]  B. Björlenius,et al.  Fluxes of 13 selected pharmaceuticals in the water cycle of Stockholm, Sweden. , 2011, Water science and technology : a journal of the International Association on Water Pollution Research.

[42]  W. Wiseman,et al.  Comparison of continuous records of near-bottom dissolved oxygen from the hypoxia zone along the Louisiana coast , 1994 .

[43]  S. Trapp,et al.  Acute Toxicity of the Dissociating Veterinary Antibiotics Trimethoprim to Willow Trees at Varying pH , 2010, Bulletin of environmental contamination and toxicology.

[44]  M. Pardal,et al.  Zooplankton and ichthyoplankton communities in a temperate estuary: spatial and temporal patterns , 2006 .

[45]  J. Zhou,et al.  Occurrence and phase distribution of selected pharmaceuticals in the Yangtze Estuary and its coastal zone. , 2011, Journal of hazardous materials.

[46]  B. Brooks,et al.  Water Quality of Effluent-dominated Ecosystems: Ecotoxicological, Hydrological, and Management Considerations , 2006, Hydrobiologia.

[47]  Daniel J Caldwell,et al.  An integrated approach for prioritizing pharmaceuticals found in the environment for risk assessment, monitoring and advanced research. , 2014, Chemosphere.

[48]  Kyungho Choi,et al.  Potential ecological footprints of active pharmaceutical ingredients: an examination of risk factors in low-, middle- and high-income countries , 2014, Philosophical Transactions of the Royal Society B: Biological Sciences.

[49]  Gerald T Ankley,et al.  Repeating history: pharmaceuticals in the environment. , 2007, Environmental science & technology.

[50]  Alistair B A Boxall,et al.  Pharmaceuticals and personal care products: Research needs for the next decade , 2009, Environmental toxicology and chemistry.

[51]  Amber Wutich,et al.  Assessment of De Facto Wastewater Reuse across the US: trends between 1980 and 2008. , 2013, Environmental science & technology.

[52]  W. Vyverman,et al.  Spatial and Temporal Dynamics of Phytoplankton Communities in a Freshwater Tidal Estuary (Schelde, Belgium) , 2000 .

[53]  J. Cook,et al.  A Theoretical Model for Utilizing Mammalian Pharmacology and Safety Data to Prioritize Potential Impacts of Human Pharmaceuticals to Fish , 2003 .

[54]  L. Henderson.  THE THEORY OF NEUTRALITY REGULATION IN THE ANIMAL ORGANISM , 1908 .

[55]  J. Nichols,et al.  Branchial elimination of superhydrophobic organic compounds by rainbow trout (Oncorhynchus mykiss). , 2001, Aquatic toxicology.

[56]  L. Cahoon,et al.  Short-term variability of water quality parameters in two shallow estuaries of North Carolina , 1999 .

[57]  T. Kratz,et al.  Annual Patterns in Bacterioplankton Community Variability in a Humic Lake , 2004, Microbial Ecology.

[58]  Gerald T Ankley,et al.  International scientists' priorities for research on pharmaceutical and personal care products in the environment , 2014, Integrated environmental assessment and management.

[59]  Alejandro J. Ramirez,et al.  Occurrence of pharmaceuticals and personal care products in fish: Results of a national pilot study in the united states , 2009, Environmental toxicology and chemistry.

[60]  C. Chambliss,et al.  Evaluation of an isotope dilution liquid chromatography tandem mass spectrometry method for pharmaceuticals in fish. , 2012, Journal of chromatography. A.

[61]  S. Maberly.  Diel, episodic and seasonal changes in pH and concentrations of inorganic carbon in a productive lake , 2008 .

[62]  B. Brooks,et al.  Human Pharmaceuticals in the Environment: Current and Future Perspectives , 2012 .

[63]  Jason P. Berninger,et al.  Leveraging existing data for prioritization of the ecological risks of human and veterinary pharmaceuticals to aquatic organisms , 2014, Philosophical Transactions of the Royal Society B: Biological Sciences.