The Sinos River is an important water supply in Southern Brazil and receives industrial, agricultural, and domestic effluents which may affect aquatic biota. Water physicochemical and microbiological analyses, biomarker responses (scaled mass index (SMI), gill histopathology, and micronucleus and nuclear abnormality (MN and NA) frequencies), and metal bioaccumulation in muscle were assessed in the fish species Bryconamericus iheringii (Characidae) captured at three sampling sites (S1, S2, and S3) in four sampling periods. The mean values of five parameters (total phosphorus, thermotolerant coliforms, aluminum, iron, and lead) exceeded the limits established by the Brazilian legislation at the three sampling sites. Although physicochemical analysis indicated higher impacts at S3, in some samples, significantly higher MN frequencies and bioaccumulation of manganese in fish muscle were observed at S1, whereas low SMI and higher concentrations of aluminum and zinc in fish muscle were found at S2. Histopathological alterations in gills were observed in fish collected at the three sampling sites; however, no spatial differences were observed, indicating similar environmental conditions with respect to this biomarker. Moreover, temporal variation of biomarker responses and metal bioaccumulation were found at all sampling sites. Furthermore, the consumption of fish from the Sinos River should be avoided given the concentrations of chromium (all samples), cadmium, and lead in fish muscle above the threshold for safe human consumption.
Considering the relation between systemic exposure to these drug and clinical responses, a posteriori TDM, with measurement of drug concentrations in plasma of treated patients, is currently the most straightforward approaches for dose individualization of paclitaxel and docetaxel.
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