Quantitative Property-Property Relationship for Screening-Level Prediction of Intrinsic Clearance of Volatile Organic Chemicals in Rats and Its Integration within PBPK Models to Predict Inhalation Pharmacokinetics in Humans

Table 7

Reliability analysis for the chemicals in the QPPR evaluation dataset.

		Impact of metabolism on AUC (AUC𝐸min/AUC𝐸max)^a
		Low (<2)	Medium (2–5)	High (>5)
	Low (<2)
QPPR prediction uncertainty (Pred./Exp. 𝐶𝐿intPL)^b	Medium (2–5)
	High (>5)	Ethylene; propylene; 1,1,1-trichloroethane	Bromoform; dibromochloromethane; trans-1,2-dichloroethylene; furan; halothane; tetrachloroethylene; 1,2,4-trimethylbenzene; o-xylene

^a Calculated as the ratio of the PBPK simulations of 24 h AUC (of venous blood concentration, 1 ppm VOC, 24 h exposure) obtained by setting 𝐸=0 (i.e., 𝐶𝐿_int=0) to that setting 𝐸=1 (i.e., 𝐶𝐿_int=1000).
^b Calculated as the ratio of the predicted to the experimental values of 𝐶𝐿_intPL.