Defining the Relative Potency of Pyrrolizidine Alkaloid N-oxides by New Approach Methodologies

Summary

Pyrrolizidine alkaloid N-oxides (PANOs) and their parent alkaloids (PAs) are plant toxins found in food and environment. In plants, PANOs are the predominant version, and when consumed, PANOs can be converted to parent PAs that are more toxic. But to date, the relative potency of PANOs compared to parent PAs are not yet clear. So we studied this using computer model and fractions of liver and fecal samples, representing parts of the body where PANOs conversion to PAs take place. We found that the relative potency value is not just a single number – rather, the value depends on many factors such as kinetics, dose, endpoint, structure and interindividual differences. At low dose level, the relative potency of PANOs is only affected by interindividual differences. We propose that the value at low dose level should be used for risk assessment, representing value that is more realistic for human exposure scenario.