Theodore W. Valenti

Aquatic toxicity of sertraline to Pimephales promelas at environmentally relevant surface water pH

Researchers recognize that ionization state may influence the biological activity of weak acids and bases. Dissociation in aqueous solutions is controlled by the pKa of a compound and the pH of the matrix. Because many pharmaceuticals are implicitly designed as ionizable compounds, site-specific variability in pH of receiving waters may introduce uncertainty to ecological risk assessments. The present study employed 48-h and 7-d toxicity tests with Pimephales promelas exposed to the model weak base pharmaceutical sertraline over a gradient of environmentally relevant surface water pHs. The 48-h experiments were completed in triplicate, and the average lethal concentration values were 647, 205, and 72 microL sertraline at pH 6.5, 7.5, and 8.5, respectively. Survivorship, growth, and feeding rate (a nontraditional endpoint linked by other researchers to sertralines specific mode of action) were monitored during the 7-d experiment. Adverse effects were more pronounced when individuals were exposed to sertraline at pH 8.5 compared to pH 7.5 and 6.5. The pH-dependent toxicological relationships from these studies were related to in-stream pH data for two streams in the Brazos River basin of central Texas, USA. This predictive approach was taken because of the scarcity of environmental analytical data for sertraline. The results of this study emphasized temporal variability associated with in-stream pH linked to seasonal differences within and between these spatially related systems. Relating site-specific pH variability of surface waters to ionization state may allow researchers to reduce uncertainty during ecological risk assessment of pharmaceuticals by improving estimates of biological effects associated with exposure.

Effects of the antihistamine diphenhydramine on selected aquatic organisms

In recent years pharmaceuticals have been detected in aquatic systems receiving discharges of municipal and industrial effluents. Although diphenhydramine (DPH) has been reported in water, sediment, and fish tissue, an understanding of its impacts on aquatic organisms is lacking. Diphenhydramine has multiple modes of action (MOA) targeting the histamine H1, acetylcholine (ACh), and 5-HT reuptake transporter receptors, and as such is used in hundreds of pharmaceutical formulations. The primary objective of this study was to develop a baseline aquatic toxicological understanding of DPH using standard acute and subchronic methodologies with common aquatic plant, invertebrate, and fish models. A secondary objective was to test the utility of leveraging mammalian pharmacology information to predict aquatic toxicity thresholds. The plant model, Lemna gibba, was not adversely affected at exposures as high as 10 mg/L. In the fish model, Pimephales promelas, pH affected acute toxicity thresholds and feeding behavior was more sensitive (no-observed-effect concentration = 2.8 µg/L) than standardized survival or growth endpoints. This response threshold was slightly underpredicted using a novel plasma partitioning approach and a mammalian pharmacological potency model. Interestingly, results from both acute mortality and subchronic reproduction studies indicated that the model aquatic invertebrate, Daphnia magna, was more sensitive to DPH than the fish model. These responses suggest that DPH may exert toxicity in Daphnia through ACh and histamine MOAs. The D. magna reproduction no-observed-effect concentration of 0.8 µg/L is environmentally relevant and suggests that additional studies of more potent antihistamines and antihistamine mixtures are warranted.

A mechanistic explanation for pH-dependent ambient aquatic toxicity of Prymnesium parvum carter

The harmful algal bloom species Prymnesium parvum has caused millions of dollars in damage to fisheries around the world. These fish kills have been attributed to P. parvum releasing a mixture of toxins in the water. The characterized toxins, reported as prymnesin-1 and -2, have structural similarities consistent with other known ionizable compounds (e.g., ammonia). We investigated whether pH affects the toxicity of P. parvum under conditions representative of inland Texas reservoirs experiencing ambient toxicity from bloom formation. We evaluated pH influences on toxicity in laboratory and field samples, and modeled the physicochemical properties of prymnesins. Aquatic toxicity to a model fish and cladoceran was reduced by lowering pH in samples obtained from reservoirs experiencing P. parvum blooms; similar observations were confirmed for experiments with laboratory cultures. A pKa value of 8.9 was predicted for the prymnesins, which suggests that ionization states of these toxins may change appreciably over surface water pH of inland waters. These findings indicate that ionization states of toxins released by P. parvum may strongly influence site-specific toxicity and subsequent impacts to fisheries. Consequently, these results emphasize the importance of understanding processes that affect pH during P. parvum blooms, which may improve predictions of ambient toxicity.

Influence of drought and total phosphorus on diel pH in wadeable streams: implications for ecological risk assessment of ionizable contaminants.

Climatological influences on site-specific ecohydrology are particularly germane in semiarid regions where instream flows are strongly influenced by effluent discharges. Because many traditional and emerging aquatic contaminants, such as pharmaceuticals, are ionizable, we examined diel surface water pH patterns (i.e., change in pH over a 24-h period) at 23 wadeable streams in central Texas, USA, representing a gradient of nutrient enrichment during consecutive summers of 2006 and 2007. The years of our study were characterized by decidedly different instream flows, which likely affected production:respiration dynamics and led to distinctions in diel pH patterns between 2006 and 2007. Site-specific ambient water quality criteria for NH(3) and the aquatic toxicity of the model weak base pharmaceutical sertraline were predicted using continuous water quality monitoring data from the sites. Drought conditions of 2006 significantly increased (p<0.05) diel pH changes compared to high instream flows of 2007,and the magnitude of diel pH variability was most pronounced at nutrient-enriched sites in 2006. Differences in diel pH change patterns between 2006 and 2007 affected predictions of the environmental fate and effects for model weak base pharmaceuticals and NH(3). Overall, site-specific diel pH was more variable at some sites than the difference in mean surface water pH between the 2 summers. Diel pH variability affected regulatory criteria, because 20% of the study sites in 2006 experienced greater than 5-fold differences in National Ambient Water Quality Criteria for NH(3) over 24-h periods. Our study emphasizes the potential uncertainty that diel pH variability may introduce in site-specific assessments and provides recommendations for environmental assessment of ionizable contaminants.

Similar anxiolytic effects of agonists targeting serotonin 5-HT1A or cannabinoid CB receptors on zebrafish behavior in novel environments

The discovery that selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine are present and bioaccumulate in aquatic ecosystems have spurred studies of fish serotonin transporters (SERTs) and changes in SSRI-sensitive behaviors as adverse outcomes relevant for risk assessment. Many SSRIs also act at serotonin 5-HT1A receptors. Since capitalizing on this action may improve treatments of clinical depression and other psychiatric disorders, novel multimodal drugs that agonize 5-HT1A and block SERT were introduced. In mammals both 5-HT1A and CB agonists, such as buspirone and WIN55,212-2, reduce anxious behaviors. Immunological and behavioral evidence suggests that 5-HT1A-like receptors may function similarly in zebrafish (Danio rerio), yet their pharmacological properties are not well characterized. Herein we compared the density of [(3)H] 8-hydroxy-2-di-n-propylamino tetralin (8-OH-DPAT) binding to 5-HT1A-like sites in the zebrafish brain, to that of similarly Gαi/o-coupled cannabinoid receptors. [(3)H] 8-OH-DPAT specific binding was 176±8, 275±32, and 230±36fmol/mg protein in the hypothalamus, optic tectum, and telencephalon. [(3)H] WIN55,212-2 binding density was higher in those same brain regions at 6±0.3, 5.5±0.4 and 7.3±0.3pm/mg protein. The aquatic light-dark plus maze was used to examine behavioral effects of 5-HT1A and CB receptor agonists on zebrafish novelty-based anxiety. With acute exposure to the 5-HT1A partial-agonist buspirone (50mg/L), or dietary exposure to WIN55,212-2 (7μg/week) zebrafish spent more time in and/or entered white arms more often than controls (p<0.05). Acute exposure to WIN55,212-2 at 0.5-50mg/L reduced mobility. These behavioral findings suggest that azipirones, like cannabinoid agonists, have anxiolytic and/or sedative properties on fish in novel environments. These observations highlight the need to consider potential ecological risks of azapirones and multimodal antidepressants in the future.

Fish-mediated nutrient cycling and benthic microbial processes: can consumers influence stream nutrient cycling at multiple spatial scales?

Abstract.  Fish-mediated nutrient recycling influences nutrient dynamics in stream ecosystems, but its consequences for smaller-scale microbial processes in benthic habitats are not well understood. We quantified the effect of nutrient recycling by the grazing fish, Campostoma anomalum, on downstream periphyton in 12 flow-through stream mesocosms. We compared periphyton nutrient ratios and algal biomass (as chlorophyll a [chl a]) between tiles upstream and downstream of enclosures with and without fish to measure nutrient-cycling effects in streams with low (11) and high (177) surface-water dissolved N∶P molar ratios. No upstream–downstream changes in periphyton nutrient ratios were observed in low N∶P streams with or without fish. In high N∶P streams, periphyton C∶N decreased and C∶P and N∶P increased on tiles downstream of enclosures. In high N∶P streams, downstream changes in periphyton nutrient ratios were greater in streams with than without fish, and chl a significantly increased downstream of enclosures with fish. We linked nutrient-recycling effects to downstream microbial processes by comparing bacterial biomass production (BBP), photosynthesis (PS) rates, and the degree of coupling between the 2 processes on tiles downstream of enclosures. We estimated the degree of coupled production between algae and bacteria downstream of enclosures as the covariance between PS and BBP among replicates within each stream (COVPS–BBP). In high N∶P streams, areal BBP and PS rates and COVPS–BBP were higher downstream of enclosures with fish. Chl a and COVPS–BBP declined with increasing periphyton C∶N content, resulting in a positive relationship between COVPS–BBP and algal biomass across all treatments. Our results indicate that grazing fish alter stream ecosystem N and P dynamics through consumer-mediated recycling pathways, but downstream responses depend on background nutrient regimes. Fish-mediated changes in nutrient dynamics and algal biomass influence reliance of heterotrophs and autotrophs on nutrients recycled within periphyton communities to support benthic production.

Ammonium treatments to suppress toxic blooms of Prymnesium parvum in a subtropical lake of semi-arid climate: results from in situ mesocosm experiments.

Prymnesium parvum is a haptophyte alga that forms toxic, fish-killing blooms in a variety of brackish coastal and inland waters. Its abundance and toxicity are suppressed by ammonium additions in laboratory cultures and aquaculture ponds. In a cove of a large reservoir (Lake Granbury, Texas, USA) with recurring, seasonal blooms of P. parvum, ammonium additions were tested in mesocosm enclosures for their ability to suppress blooms and their effects on non-target planktonic organisms. One experiment occurred prior to the peak abundance of a P. parvum bloom in the cove, and one encompassed the peak abundance and decline of the bloom. During 21-day experiments, weekly doses raised ammonium concentrations by either 10 or 40 μM. The added ammonium accumulated in experimental mesocosms, with little uptake by biota or other losses. Effects of ammonium additions generally increased over the course of the experiments. The higher ammonium dose suppressed the abundance and toxicity of P. parvum. The biomass of non-haptophyte algae was stimulated by ammonium additions, while positive, negative and neutral effects on zooplankton taxa were observed. Low ammonium additions insufficient to control P. parvum exacerbated its harmful effects. Our results indicate a potential for mitigating blooms of P. parvum with sufficient additions of ammonium to coves of larger lakes. However, factors excluded from mesocosms, such as dilution of ammonium by water exchange and sediment ammonium uptake, could reduce the effectiveness of such additions, and they would entail a risk of eutrophication from the added nitrogen.