Influence of salinity and pH on bioconcentration of ionizable pharmaceuticals by the gulf killifish, Fundulus grandis

Estuaries routinely receive discharges of contaminants of emerging concern from urban regions. Within these dynamic estuarine systems, salinity and pH can vary across spatial and temporal scales. Our previous research identified bioaccumulation of the calcium channel blocker diltiazem and the antihistamine diphenhydramine in several species of fish residing in multiple urban estuaries along the Gulf of Mexico in Texas, where field-measured observations of diltiazem in fish plasma exceeded human therapeutic plasma doses. However, there remains a limited understanding of pharmaceutical bioaccumulation in estuarine environments. Here, we examined the influence of pH and salinity on bioconcentration of three pharmaceuticals in the Gulf killifish, Fundulus grandis. F. grandis were exposed to low levels of the ionizable pharmaceuticals carbamazepine, diltiazem, and diphenhydramine at two salinities (5 ppt, 20 ppt) and two pH levels (6.7, 8.3). pH influenced bioconcentration of select weak base pharmaceuticals, while salinity did not, suggesting that intestinal uptake via drinking does not appear to be a major exposure route of these pharmaceuticals in killifish. Compared to our previous pH dependent uptake observations with diphenhydramine in the fathead minnow model, killifish apparent volume of distribution values were markedly lower than fatheads, though killifish bioconcentration factors were similar at high pH and four fold higher at low pH than freshwater fish. Advancing an understanding of environmental gradient influences on pharmacokinetics among fish is necessary to improve bioaccumulation assessments and interpretation of toxicological observations for ionizable contaminants.