Bioaccumulation and tissue distribution of pharmaceuticals and their transformation products in fish along the pollution gradients of a wastewater-impacted river.

A field study on the occurrence and distribution of forty-three pharmaceutically active compounds (PhACs) in water and fish samples from anthropogenically impacted section of the Sava River (Croatia) was performed to estimate the importance of bioaccumulation for the environmental risk assessment of PhACs. The study was performed using a highly specific LC-MS/MS method, tailored to include the most prominent PhACs from different therapeutic categories as well as their major metabolites and/or transformation products (TPs). The results revealed a widespread occurrence of PhAC residues both in water and fish samples with a large spatial variability reflecting the distance from the dominant wastewater discharges. The most prominent PhAC categories in less polluted upstream part of the river were common psychostimulants caffeine and cotinine, therapeutic opioids and cardiovascular drugs, while in the river section affected by the local municipal and industrial wastewater inputs, antibiotic drugs became clearly predominant, especially in fish tissue samples. The apparent bioconcentration factors (BCFs) of investigated PhACs varied over several orders of magnitude, from 0.02 ± 0.01 L kg^-1 for O-desmethyl tramadol in fish muscle to 784 ± 260 L kg^-1 for terbinafine in fish liver, indicating rather large differences in their bioconcentration potential and affinity to different tissues, with the tissue-specific BCFs increasing in the following order: muscle < gills < gonads < heart < liver < kidneys. The bioconcentration potential of most of the PhACs included in this study was only low to moderate however moderately high BCFs of certain PhACs (e.g. sertraline, terbinafine, loratadine, diazepam and azithromycin) in some tissues should be taken into consideration when assessing their potential environmental risks. Moreover, it was shown that BCFs could be strongly affected by biotransformation in fish. Risk prioritization based on risk quotient (RQ) and ToxPi index, revealed antibiotics, in particular azithromycin, and therapeutic psychoactive substances as the most hazardous pharmaceutical contaminants in the Sava River.