Upadacitinib is a pharmacologically active or chemically reactive compound used in pharmaceutical manufacturing as an active ingredient, synthetic intermediate, or process reagent, requiring toxicological characterisation to establish protective occupational exposure limits. Available data from in vitro and in vivo studies are evaluated in a weight-of-evidence assessment to identify the critical study, the most sensitive adverse effect endpoint, and the applicable NOAEL or LOAEL that serves as the point of departure for PDE calculation. Data gaps are addressed through read-across from structurally related compounds, (Q)SAR predictions, or application of TTC defaults where scientifically justified.
Reproductive and developmental toxicity findings for Upadacitinib receive an additional severity factor consideration in PDE derivation, because pharmaceutical patient populations frequently include women of childbearing potential and, in some indications, pregnant patients.