Influence of Diltiazem on Fathead Minnows Across Dissolved Oxygen Gradients

Abstract

Water resources in many arid to semi-arid regions are stressed by population growth and drought. Growing populations and climatic changes are influencing contaminant and water chemistry dynamics in urban inland waters, where flows can be dominated by, or even dependent on, wastewater effluent discharge. In these watersheds, interacting stressors such as dissolved oxygen and environmental contaminants (e.g., pharmaceuticals) have the potential to affect fish physiology and populations. Recent field observations from our group identified the calcium channel blocker (CCB) diltiazem in fish plasma exceeding human therapeutic doses (e.g., C ) in aquatic systems impaired because of nonattainment of dissolved oxygen water quality standards. Therefore our study objectives examined: 1) standard acute and chronic effects of dissolved oxygen and diltiazem to fish, 2) influences of dissolved oxygen at criteria levels deemed protective of aquatic life on diltiazem toxicity to fish, and 3) whether sublethal effects occur at diltiazem water concentrations predicted to cause a human therapeutic level (therapeutic hazard value [THV]) in fish plasma. Dissolved oxygen × diltiazem co-exposures significantly decreased survival at typical stream, lake, and reservoir water quality standards of 5.0 and 3.0 mg dissolved oxygen/L. Dissolved oxygen and diltiazem growth effects were observed at 2 times and 10 times lower than median lethal concentration (LC50) values (1.7 and 28.2 mg/L, respectively). Larval fathead minnow (Pimephales promelas) swimming behavior following low dissolved oxygen and diltiazem exposure generally decreased and was significantly reduced in light-to-dark bursting distance traveled, number of movements, and duration at concentrations as low as the THV. Individual and population level consequences of such responses are not yet understood, particularly in older organisms or other species; however, these findings suggest that assessments with pharmaceuticals and other cardioactive contaminants may underestimate adverse outcomes in fish across dissolved oxygen levels considered protective of aquatic life. Environ Toxicol Chem 2018;37:2835-2850. © 2018 SETAC.

A survey of fish behaviour quantification indexes and methods in aquaculture

“…Behaviour is a direct reflection of neural activity. Fish can make a series of behavioural responses to external stimuli, such as light (Karakatsouli et al 2007;Higgs et al 2018;Malambugi et al 2020), water quality (Braun & Perry 2010;Longhini et al 2017;Saari et al 2018), and breeding density (Hong et al 2019) and flow (Breitburg et al 1995). For example, some fish species can reduce irritation by moving away from light sources (Hannah et al 2015;Karlsen et al 2015;Santos et al 2019).…”

Interaction of the Olfactory System of Rainbow Trout (Oncorhynchus mykiss) with Diltiazem

“…Experimental water concentrations, plasma concentrations, and whole-body tissue concentrations for diltiazem were analytically verified by isotope dilution liquid chromatography-tandem mass spectrometry. All extractions and analysis followed previously reported methods (Du et al 2014(Du et al , 2016Bean et al 2018;Haddad et al 2018;Saari et al 2018). Briefly, 500 mL of water was collected from each exposure tank.…”

“…Fish tissue homogenates were stored at −20 °C prior to extraction and analysis. Instrument parameters are provided in detail elsewhere (Saari et al 2018). Method detection limits were 0.31 ng/L for water, 0.06 µg/kg for tissue, and 0.06 ng/mL for plasma.…”

“…Such observations are important because fish plasma modeling, in which human plasma doses of therapeutic responses and side effects are compared to exceedance predictions in fish, appears useful for prioritizing pharmaceuticals for aquatic risks to fish (Huggett et al 2003;Fick et al 2010;Brooks 2014). Several recent studies have subsequently studied uptake and responses of several fish species to diltiazem (Saari et al 2018(Saari et al , 2020Scott et al 2019).…”

Factors Affecting the Binding of Diltiazem to Rainbow Trout Plasma: Implications for the Risk Assessment of Pharmaceuticals in Aquatic Systems

“…Field studies have shown that fish plasma diltiazem concentrations can exceed human plasma therapeutic values (Saari et al, 2017; Scott et al, 2016), indicating the potential for biological effects. In fish, diltiazem effects include impaired behavior (Saari et al, 2018), altered antioxidant status, modifications in key enzyme activities, and histological damage to tissues (Steinbach, Burkina, et al, 2016), while diltiazem also exacerbates the effects of low dissolved oxygen on swimming performance in fathead minnows (Saari et al, 2020). Critically, measured plasma diltiazem concentrations in field‐collected fish can exceed those predicted by modelling by more than an order of magnitude (Scott et al, 2016).…”