Exposure margins in toxicology
An exposure margin compares exposure at a defined nonclinical dose with exposure under a specified human regimen.
An exposure margin compares exposure at a defined nonclinical dose with exposure under a specified human regimen (ICH. S3A: The Assessment of Systemic Exposure in Toxicity Studies. 1994.).
For example, animal AUC of 120 mg·h/L divided by human AUC of 30 mg·h/L gives a fourfold AUC margin. Identify the animal finding or dose level used and the human exposure statistic. Check species differences in protein binding and metabolites before interpreting the ratio. A fourfold AUC margin does not by itself establish a safety threshold.