Individual and interactive influences of low dissolved oxygen and calcium channel blockers in inland aquatic systems.

Understanding and managing influences of multiple stressors represents a major water quality challenge, particularly in urbanizing regions. Because aquatic hazard assessments with chemical and nonchemical stressors can identify the global trends in occurrence and hazards of stressors for the protection of aquatic life, probabilistic aquatic hazard assessments were performed to examine whether water quality guidelines for dissolved oxygen (DO) are protective of aquatic life in inland waters. My analyses indicate that adverse effects of low DO to freshwater invertebrates and fish have been underestimated in inland waters. Additional low DO threshold information, including sublethal toxicity, for additional species such as warm water fish and mollusks across multiple life history stages is necessary to support environmental assessment and management of ecosystem protection goals. Similar techniques were used to examine the occurrence of calcium channel blockers (CCBs), a common class of vasodilators and cardio suppressants, in environmental matrices, and to predict hazards to non-target aquatic organisms in multiple environmental matrices and geographic regions. Whereas environmental occurrence of CCBs in freshwater and effluent have predominantly been reported from North America and Europe, data is lacking from many developing regions around the world and hazards and risks of CCBs to non-target biota remains poorly understood. Therapeutic hazard values (THVs), a comparative pharmacology and toxicology approach, employed during probabilistic hazard assessments with environmental exposure distributions revealed that amlodipine and verapamil in effluent and freshwater exceeded THVs 28% of the time. Diltiazem exceeded minimum human therapeutic thresholds in fish plasma ~18% of the time in surface waters. This approach demonstrated the utility of global assessments to identify specific CCBs and geographic regions where environmental assessments appear necessary. Subsequently, to understand adverse effects of individual and multiple stressors influencing cardiac function (DO, diltiazem, or DO x diltiazem), toxicity studies were performed using a comparative toxicology and pharmacology approach in fathead minnows (Pimephales promelas) across larval and adult life stages. DO x diltiazem toxicity studies with larval fish revealed acute lethality increased with decreasing DO levels and altered burst swimming behavior at DO water quality criteria levels deemed protective of aquatic life. In adult fathead minnows, low DO (3.0 mg DO/L) increased uptake of diltiazem and altered physiological responses (e.g., hematocrit, plasma lactate) at and above human therapeutic plasma levels. Failing to consider low DO influences with chemical exposure during toxicological studies of cardioactive medications and potentially other cardiotoxicants underestimates adverse outcomes in fish.