Complex mixtures, complex responses: Assessing pharmaceutical mixtures using field and laboratory approaches

Abstract

Pharmaceuticals are present in low concentrations (<100 ng/L) in most municipal wastewater effluents but may be elevated locally because of factors such as input from pharmaceutical formulation facilities. Using existing concentration data, the authors assessed pharmaceuticals in laboratory exposures of fathead minnows (Pimephales promelas) and added environmental complexity through effluent exposures. In the laboratory, larval and mature minnows were exposed to a simple opioid mixture (hydrocodone, methadone, and oxycodone), an opioid agonist (tramadol), a muscle relaxant (methocarbamol), a simple antidepressant mixture (fluoxetine, paroxetine, venlafaxine), a sleep aid (temazepam), or a complex mixture of all compounds. Larval minnow response to effluent exposure was not consistent. The 2010 exposures resulted in shorter exposed minnow larvae, whereas the larvae exposed in 2012 exhibited altered escape behavior. Mature minnows exhibited altered hepatosomatic indices, with the strongest effects in females and in mixture exposures. In addition, laboratory-exposed, mature male minnows exposed to all pharmaceuticals (except the selective serotonin reuptake inhibitor mixture) defended nest sites less rigorously than fish in the control group. Tramadol or antidepressant mixture exposure resulted in increased splenic T lymphocytes. Only male minnows exposed to whole effluent responded with increased plasma vitellogenin concentrations. Female minnows exposed to pharmaceuticals (except the opioid mixture) had larger livers, likely as a compensatory result of greater prominence of vacuoles in liver hepatocytes. The observed alteration of apical endpoints central to sustaining fish populations confirms that effluents containing waste streams from pharmaceutical formulation facilities can adversely impact fish populations but that the effects may not be temporally consistent. The present study highlights the importance of including diverse biological endpoints spanning levels of biological organization and life stages when assessing contaminant interactions.

Effects of urban stormwater and iron‐enhanced sand filtration on Daphnia magna and Pimephales promelas

“…Interestingly, the presence and total concentrations of CECs (Figure ; Fairbairn et al ) appeared to have little impact on the observed patterns of biological responses in fathead minnow bioassays. Even though prior studies (Painter et al ; Schoenfuss et al ) found reduced predator escape performance in the presence of elevated pharmaceutical and estrogenic contamination, fathead minnow feeding, growth, and escape performance were among the highest responses in early summer samples despite the relatively enhanced presence of pharmaceuticals and pesticides, many of which are known estrogens (Figure C and Table ; Fairbairn et al ). Even mean total CEC concentration, which was second highest in the early summer samples, did not appear to affect the fathead minnow bioassays.…”

“…Fathead minnow were obtained from Environmental Testing and Consulting. All exposures began with larvae <24 h post hatch and lasted 21 d following established protocols (Painter et al ; Schoenfuss et al ). Larval fish were randomly distributed to 1‐L treatment jars (3 jars/treatment, 20 larvae/jar) each containing 0.6 L stormwater.…”

“…Males were identified by enlarged antennules (Ebert 2005). Larval performance assays were based on published protocols (Painter et al 2009;Schoenfuss et al 2016). At the end of the 21-d exposure period, larvae predator escape performance was recorded with a RedLake MotionScope M1 at 1000 fps.…”

Endocrine disruption in aquatic systems: up‐scaling research to address ecological consequences

“…Wastewater effluents and other pollutant sources are often composed of highly complex mixtures, and interactions between EDCs and of EDCs with other chemicals could alter their biological effects (Keiter et al, 2012;Schoenfuss et al, 2015). The potential for additive effects of EDCs and other chemicals is significant.…”

“…Over the past decade published work on EDCs has provided a strong mechanistic understanding of exposure effects (Colborn, vom Saal & Soto, 1993;Tyler, Jobling & Sumpter, 1998;Kloas et al, 2009;Orton & Tyler, 2012;Tijani, Fatoba & Petrik, 2013). Far less consideration, however, has been given to processes and interactions controlling the effects of EDCs at broader ecological scales, including inter-and intra-specific interactions within populations and food webs (Segner, 2011;Brodin et al, 2014;Schoenfuss et al, 2015). Understanding the effects of EDCs on processes operating at these broader scales is essential, but also challenging, because their effects can be pervasive and they are generally sub-lethal in nature.…”