Comparative analysis of in vivo and in silico toxicity evaluation of the organoiodine compounds towards D. magna using multivariate chemometric approach: A study on the example of amiodarone phototransformation products

In the present study the photochemical fate of organoiodine compound - amiodarone was performed. The drug turned out to be highly susceptible to UV-Vis irradiation, especially in the presence of humic substances and organic matrix. Qualitative LC-MS analysis revealed formation of twelve - mainly previously unreported - transformation products (TPs). Four major TPs were submitted to the toxicity analysis with the use of D. magna. All of the tested TPs presented higher toxic potential than the parent compound. The phenolic TPs were approximately 100 times more toxic than amiodarone. Toxic properties of the major TPs resulted in steadily increasing toxic potential of the photo-generated mixture over the time of irradiation. Moreover, the experimental toxicity data, concerning the TPs, were compared with results estimated by 6 in silico models with the use of a multivariate chemometric analysis. The results showed that the applied computational methods were able neither to correctly predict toxic properties of the studied compounds, nor the trends in change of their toxic parameters. Additional validation of in silico models ability to predict toxicity of iodinated organic compounds showed that the studied computational methods do not present sufficient prediction ability. Therefore their estimations concerning organoiodines should be verified using experimental tests.

Automated summary

This study investigated the photochemical fate of the organoiodine compound - amiodarone. The results showed that the drug is highly susceptible to UV-Vis irradiation, especially in the presence of humic substances and organic matrix. Twelve transformation products (TPs), most of which were previously unreported, were identified through qualitative LC-MS analysis. Four major TPs were found to be more toxic than the parent compound, with phenolic TPs being approximately 100 times more toxic than amiodarone. In silico models were unable to accurately predict the toxic properties and trends of the studied compounds, highlighting the need for experimental validation.