Laboratory of Innovative Toxicological Research and Analyses, Institute of Medical Sciences, Medical College, Rzeszów University, Al. mjr. W. Kopisto 2a, 35-959 Rzeszów, Poland.
Department of Regulatory and Forensic Toxicology, Institute of Medical Expertise, Łódź, ul. Aleksandrowska 67/93, 91-205 Łódź, Poland.
Int J Mol Sci. 2024 May 28;25(11):5867. doi: 10.3390/ijms25115867.
This study reports the first application of in silico methods to assess the toxicity of 4-chloromethcathinone (4-CMC), a novel psychoactive substance (NPS). Employing advanced toxicology in silico tools, it was possible to predict crucial aspects of the toxicological profile of 4-CMC, including acute toxicity (LD), genotoxicity, cardiotoxicity, and its potential for endocrine disruption. The obtained results indicate significant acute toxicity with species-specific variability, moderate genotoxic potential suggesting the risk of DNA damage, and a notable cardiotoxicity risk associated with hERG channel inhibition. Endocrine disruption assessment revealed a low probability of 4-CMC interacting with estrogen receptor alpha (ER-α), suggesting minimal estrogenic activity. These insights, derived from in silico studies, are critical in advancing the understanding of 4-CMC properties in forensic and clinical toxicology. These initial toxicological findings provide a foundation for future research and aid in the formulation of risk assessment and management strategies in the context of the use and abuse of NPSs.
本研究报告了首例应用计算方法评估新型精神活性物质 4-氯甲卡西酮（4-CMC）毒性的研究。通过使用先进的毒理学计算工具，我们可以预测 4-CMC 的毒理学特征的关键方面，包括急性毒性（LD）、遗传毒性、心脏毒性以及其内分泌干扰的潜力。获得的结果表明，4-CMC 具有明显的物种特异性急性毒性，中度遗传毒性潜力表明存在 DNA 损伤的风险，以及与 hERG 通道抑制相关的显著心脏毒性风险。内分泌干扰评估表明 4-CMC 与雌激素受体 alpha（ER-α）相互作用的可能性较低，提示其雌激素活性较低。这些源自计算研究的见解对于推进法医和临床毒理学中对 4-CMC 特性的理解至关重要。这些初步的毒理学发现为未来的研究提供了基础，并有助于在新型精神活性物质的使用和滥用背景下制定风险评估和管理策略。
