In vitro-in silico study on the influence of dose, fraction bioactivated and endpoint used on the relative potency value of pyrrolizidine alkaloid N-oxides compared to parent pyrrolizidine alkaloids.

ABSTRACT: Pyrrolizidine alkaloids (PAs) and their N-oxides (PA-N-oxides) are phytotoxins found in food, feed and the environment. Yet, limited data exist from which the relative potency of a PA-N-oxide relative to its corresponding PA (REP_{PANO to PA}) can be defined. This study aims to investigate the influence of dose, fraction bioactivated and endpoint on the REP_{PANO to PA} of a series of pyrrolizidine N-oxides using in vitro-in silico data and physiologically based kinetic (PBK) modeling. The first endpoint used to calculate the REP_{PANO to PA} was the ratio of the area under the concentration-time curve of PA resulting from an oral dose of PA-N-oxide divided by that from an equimolar dose of PA (Method 1). The second endpoint was the ratio of the amount of pyrrole-pr

SUBMITTER: Alhejji Y 

PROVIDER: S-EPMC10926302 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature