| Popis: |
Anticancer drugs and their metabolites discarded in wastewater upon excretion may negatively impact the reproduction and survival of many freshwater organisms. The aim of this in silico study was to predict the ecotoxic profile of the IARC Group I anticancer drugs (n=12) and elucidate their impact on the environment and health using four ADMET PredictorTM models: the fathead minnow acute toxicity model based on lethal effects on Pimephales promelas (Minnow LC50, TOX_FHM), the concentration needed to inhibit 50 % of growth in the protozoa species Tetrahymena pyriformis (Th_pyr_pIGC50), the lethal concentration that results in the death of 50 % of Daphnia magna (water fleas) (Daphnia_LC50, TOX_DM) and the bioconcentration factor (BCF). The obtained results revealed the non-biodegradability of all molecules with the bioconcentration factor (BCF) computed in the range from 1.781 (thiotepa) to 175.844 (tamoxifen). Toxicities to the fathead minnow were computed in the range of Minnow_LC50 0.002 (4-OH-tamoxifen and 4-OH-desmethyltamoxifen) to 3611.004 mg/mL (busulfan), toxicities to Tetrahymena pyriformis were computed in the range of Th_Pyr_pIGC50, from 0.503 (thiotepa) to 2.366 mmol/L (tamoxifen), whereas toxicities to Daphnia magna were in the range of Daphnia_LC50 0.069 (4- OH-desmethyltamoxifen) to 2047.628 mg/L (busulfan). QSAR analysis revealed a linear relationship between lipophilicity (MlogP) and Th_pyr_pIC50 (y=2.039x -0.204, R2=0.704), and hyperbolic relationship with BCF. Furthermore, mutagenicity was predicted for alkylating agents (melphalan, cyclophosphamide, busulfan, thiotepa, and semustine), carcinogenicity for cyclophosphamide, etoposide, thiotepa and semustine, cardiotoxicity for tamoxifen and its OH- and N-dealkylated metabolites, with hepatotoxicity calculated only for semustine. |
