Danio rerio embryo as in vivo model for the evaluation of the toxicity and metabolism of pyrovalerone cathinones

The objective of the present manuscript was the evaluation of the toxicity and metabolism of the second generation of pyrovalerone cathinones (α-PHP, α-PHPiP, 4-MePPP and TH-PVP), using an early zebrafish (Danio rerio) larvae as in vivo model. Pyrovalerone cathinones LC₅₀ were determined after 24, 48, 72 and 96 h of exposure. TH-PVP proved to be the most toxic cathinone, whereas 4-MePPP was the least toxic. During acute exposure to pyrovalerone cathinones the main signs of toxicity exhibited by survivors were pericardial edema, yolk sac in embryos, bradycardia, delay in the hatching, malformations, and larvae without touch response. Afterwards, a short-term non-lethal experiment (24 h) was performed with early zebrafish larvae (72 h) for each of the selected compounds. The produced metabolites were tentatively identified by liquid chromatography-high resolution mass spectrometry (LC-HRMS) and the metabolic pathways were proposed. The results showed that hydroxylation and dihydroxylation can be considered the main metabolic pathways, although depending of the cathinone studied, other metabolites can be found.