The influence of the UV-Vis radiation on the toxicity of agomelatine, loxapine, clozapine and tiapride was studied. The phototransformation procedure was conducted with the use of simulated solar radiation. In the case of each compound irradiation time necessary to decompose half of the initial concentration was chosen. The embryotoxicity and acute toxicity were evaluated using zebrafish (Danio rerio) embryos and larvae. The mutagenicity assay was done with the use of a micro-plate Ames test. Generally, the embryotoxicity decreased after the irradiation procedure. The obtained results showed that tiapride is the least toxic compound to zebrafish, however, its toxicity toward larvae increases after the irradiation. Similarly, the mutagenic potential of the mixture of tiapride photoproducts is higher than in the case of parent compound. The phototransformation of loxapine resulted in the change of the acute toxicity profile and increased the rate of reverse mutations in the Ames test. Oppositely, the irradiation of agomelatine caused the decrease of mutagenic potential and acute toxicity was also lower in the postirradiated mixture. The phototransformation of clozapine did not alter the mutagenicity and decreased the acute toxicity to the zebrafish larvae. In silico calculations showed a satisfactory prediction ability in some instances, especially in the case of mutagenic potential of the tiapride phototransformation products.
Keywords: S. typhimurium TA100; Ames test; Danio rerio; Embryotoxicity; In silico toxicity; Photodegradation.