In silico prediction of the fate and toxic effects of IARC Group I anticancer drugs in the environment (CROSBI ID 710445)
Prilog sa skupa u časopisu | sažetak izlaganja sa skupa | međunarodna recenzija
Podaci o odgovornosti
Milena, Jadrijević-Mladar Takač ; Irena, Žuntar ; Tin, Takač
engleski
In silico prediction of the fate and toxic effects of IARC Group I anticancer drugs in the environment
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.
ADMET ; bioconcentration factor ; Daphnia magna ; Pimephales promalis ; Tetrahymena pyriformis ; toxicity prediction tests
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Podaci o prilogu
76-76.
2021.
nije evidentirano
objavljeno
Podaci o matičnoj publikaciji
Arhiv za higijenu rada i toksikologiju
Lyons, Daniel Mark
Zagreb: Institut za medicinska istraživanja i medicinu rada
0004-1254
1848-6312
Podaci o skupu
6th Croatian congress of toxicology with international participation (CROTOX 2021)
poster
03.06.2021-06.06.2021
Rabac, Hrvatska