Factors influencing chemical relative potency in mixture toxicity risk assessment

Abstract

The concept of relative potency (REP) is well established through terms like REP, relative potency factor (RPF), and toxic equivalency factor (TEF). REP is often determined using in vivo data, such as for dioxins. However, many factors such as dose, species, endpoint, interindividual variability, and chemical structure can influence REP values. This mini review examines REP values for pyrrolizidine alkaloid N-oxides (PA-N-oxides) versus their parent alkaloids. Using physiologically based kinetic (PBK) model simulations, the impact of dose, species, endpoint, interindividual variability, and chemical structure on REP values could be quantified. Results show that interindividual variability and chemical structure are the most influential. This highlights PBK modeling as a valuable tool for predicting REP, especially when animal data are limited and in vitro tests alone are insufficient.