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 4

Reliability analysis of the QPPR for 𝐶𝐿_𝑖𝑛𝑡 on the PBPK predicted AUC.

		Impact of metabolism on AUC (AUC𝐸min/AUC𝐸max)^a
		Low (<2)	Medium (2–5)	High (>5)
QPPR prediction uncertainty (Pred./Exp. CLintPL)^b	Low (<2)	Isoprene, vinyl chloride	Benzene; bromochloromethane; bromodichloromethane; chloroform; dibromomethane; 1,2-dichloroethane; hexachloroethane; n-hexane; pentachloroethane; styrene; 1,1,1,2-tetrachloroethane; 1,1,2,2-tetrachloroethane; toluene; 1,1,2-trichloroethane; trichloroethylene; m-xylene
	Medium (2–5)	1,1,-Dichloroethylene	Carbon tetrachloride; chloroethane; 1,1-dichloroethane; cis-1,2-dichloroethylene; dichloromethane; ethylbenzene; methyl chloride
	High (>5)

^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.