Advances in Toxicity Risk Control and Modern Research of Highly Toxic Traditional Chinese Medicinal Materials

• • The 2025 Chinese Pharmacopoeia classifies highly toxic medicinal materials into a 3-tier system (highly toxic, toxic, mildly toxic), inheriting Li Shizhen's 4-tier classification from Bencao Gangmu; this regulatory framework imposes strict clinical constraints including pregnancy contraindications, compatibility禁忌, and dosage limits, directly impacting prescribing practices for over 50 identified high-toxicity compounds such as aconitine alkaloids and brucine. • • HPLC-MS-based fingerprinting has successfully identified more than 50 highly toxic constituents across these materials, enabling qualitative and quantitative analysis; this analytical capability is critical for batch-to-batch quality control, as therapeutic windows are extremely narrow—therapeutic and toxic doses are nearly identical, risking multi-organ failure and death. • • Mechanistic studies using apoptotic signaling pathways and metabolomics have uncovered 'biphasic toxicity effects,' where toxicity and efficacy are dose-dependent and interconvertible; this bidirectional toxicity-efficacy relationship necessitates precise dosage optimization to avoid therapeutic failure or adverse reactions, as demonstrated in cardiotoxicity evaluations of aconitine using heart-on-a-particle microfluidic devices. • • Traditional processing (paozhi) and compatibility (peiwu) detoxification strategies have been scientifically validated; for example, controlled processing conditions promote conversion of toxic alkaloids, significantly reducing toxicity while preserving efficacy, as shown in studies on Chuanwu where different processed products were evaluated for 'toxicity reduction-efficacy preservation,' providing a scalable approach for industrial production.