Integration of computational models to predict botanical phytochemical constituent clearance routes by the extended clearance classification system (ECCS)

The Botanical Safety Consortium has a new publication that demonstrates how computational modeling can streamline safety evaluations of botanical products. Using the Extended Clearance Classification System (ECCS), the researchers predicted how 82 phytochemicals from 13 botanicals are processed in the human body—whether through liver metabolism, hepatic uptake, or renal clearance. Over half of the constituents were classified as being predominantly metabolized by liver enzymes like CYP3A4, CYP2D6, and CYP1A2, indicating a higher potential for drug-botanical interactions. Conversely, around 20% of compounds were predicted to be cleared unchanged via the kidneys. This work provides a practical, scalable framework for predicting the absorption, distribution, metabolism, and excretion (ADME) of complex botanical mixtures, supporting more efficient risk assessments without requiring extensive animal studies. The approach aligns with emerging new approach methodologies (NAMs) and offers toxicologists a valuable tool for understanding botanical safety profiles in a regulatory context.

Integration of computational models to predict botanical phytochemical constituent clearance routes by the extended clearance classification system (ECCS). Liu et al., 2025. Toxicology and Applied Pharmacology. https://doi.org/10.1016/j.taap.2025.117385