Therapeutic Levels of Levonorgestrel Detected in Blood Plasma of Fish: Results from Screening Rainbow Trout Exposed to Treated Sewage Effluents

Abstract

Pharmaceuticals are found in surface waters worldwide, raising concerns about effects on aquatic organisms. Analyses of pharmaceuticals in blood plasma of fish could provide means to assess risk for pharmacological effects, as these concentrations could be compared with available human therapeutic plasma levels. In this study we investigated if fish exposed to sewage effluents have plasma concentrations of pharmaceuticals that are approaching human therapeutic levels. We also evaluated how well the bioconcentration of pharmaceuticals into fish blood plasma can be predicted based on lipophilicity. Rainbow trout were exposed to undiluted, treated sewage effluents at three sites in Sweden for 14 days. Levels of 25 pharmaceuticals in blood plasma and effluents were analyzed with liquid chromatography-mass spectrometry/mass spectrometry and gas chromatography-high resolution mass spectrometry. The progestin pharmaceutical levonorgestrel was detected in fish blood plasma at concentrations (8.5-12 ng mL(-1)), exceeding the human therapeutic plasma level. In total 16 pharmaceuticals were detected in fish plasma at concentrations higher than 1/1000 of the human therapeutic plasma concentration. Twenty-one pharmaceuticals were detected in either plasma or effluent, and 14 were detected in both compartments, allowing plasma bioconcentration factors to be determined. For 11 of these, theoretically calculated and experimentally measured values were in reasonably good agreement. However a few drugs, including levonorgestrel, did not bioconcentrate according to the screening model used. This study shows that rainbow trout exposed to sewage effluents have blood plasma levels of pharmaceuticals similar to human therapeutic concentrations, suggesting a risk for pharmacological effects in the fish. There is a particular concern about effects of progestin pharmaceuticals. For levonorgestrel, the measured effluent level (1 ng/L) was higher than water levels shown to reduce the fertility of fish.