First toxicity profile of aminoindane-based new psychoactive substances: 2-aminoindane (2-AI, CAS: 2975-41-9) and N-Methyl-2-aminoindane (NM-2-AI, CAS: 24445–44–1) – comprehensive prediction of toxicological endpoints important from clinical and forensic perspective using in silico multi- approach

Abstract

This study provides the first toxicity profile of two aminoindane-based new psychoactive substances (NPS): 2-aminoindane (2-AI) and N-methyl-2-aminoindane (NM-2-AI), using a multi-method in silico approach. Tools including Percepta, ProTox 3.0, ADMETlab 3.0, VEGA QSAR, TEST, QSAR Toolbox, and STopTox were applied to evaluate acute toxicity, systemic organ effects, genotoxicity, skin and eye irritation, and cardiotoxicity. Both compounds were predicted to be acutely toxic via oral, dermal, and inhalation routes. Quantitative LD₅₀ values (rat, oral) ranged from 150 to 560 mg/kg (Percepta), 259.7–112.6 mg/kg (VEGA), and 326–360 mg/kg (ProTox 3.0). Health effect predictions indicated high probabilities of cardiovascular toxicity (2-AI: 80 %, NM-2-AI: 82 %) and pulmonary involvement (66 % and 65 %, respectively). NM-2-AI showed a higher likelihood of genotoxicity (Ames test) with a probability of 66.3 % (ADMETlab), compared to 2-AI (58.7 %). Both substances were predicted to be non-irritant to the eye, but skin irritation was probable for 2-AI (80 %, StopTox) and less so for NM-2-AI (60 %). hERG inhibition risk was low (IC₅₀: 391.7 μM for 2-AI; 126.9 μM for NM-2-AI). The in silico multi-tool strategy yielded convergent and interpretable data, supporting early toxicological characterization. These results are relevant for clinical management of NPS intoxications and for forensic interpretation in the absence of experimental data.