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 3

Area under the curve for four metabolic scenarios for the VOCs used in the QPPR development.

Chemicals	24 h Area under the curve (mg/L-h)
	Metabolic scenario^a
	𝐸min	𝐸max	LMCI	UMCI
Benzene	0.437	0.125	0.155	0.138
Bromochloromethane	0.913	0.229	0.305	0.257
Bromodichloromethane	2.380	0.356	0.523	0.422
Carbon tetrachloride	0.34	0.153	0.224	0.186
Chloroethane	0.156	0.069	0.084	0.076
Chloroform	0.599	0.185	0.257	0.211
Dibromomethane	1.659	0.336	0.466	0.384
Dichloroethane (1,1-)	0.391	0.138	0.181	0.158
Dichloroethane (1,2-)	1.142	0.205	0.305	0.241
Dichloroethylene (1,1-)	6.98×10^−2	4.22×10^−2	4.76×10^−2	4.47×10^−2
Dichloroethylene (cis-1,2)	0.702	0.174	0.214	0.188
Dichloromethane	0.65	0.157	0.206	0.174
Ethylbenzene	1.247	0.216	0.32	0.246
Hexachloroethane	3.071	0.494	1.774	0.738
Hexane (n-)	0.15	0.073	0.129	0.084
Isoprene	4.59×10^−2	2.81×10^−2	0.084	2.95×10^−2
Methyl chloride	0.119	0.054	0.064	0.057
Pentachloroethane	2.584	0.418	0.929	0.595
Styrene	1.497	0.222	0.322	0.246
Tetrachloroethane (1,1,1,2-)	1.911	0.337	0.739	0.457
Tetrachloroethane (1,1,2,2-)	3.337	0.384	0.717	0.495
Toluene	0.74	0.168	0.223	0.188
Trichloroethane (1,1,2-)	1.876	0.284	0.474	0.355
Trichloroethylene	0.721	0.209	0.267	0.227
Vinyl chloride	6.68×10^−2	3.79×10^−2	4.25×10^−2	3.98×10^−2
Xylene (m-)	1.117	0.209	0.308	0.236

^a: 𝐸_min: no metabolism; 𝐸_max: maximum hepatic extraction; LMCI and UMCI: lower and upper bound of the 95% mean confidence interval, respectively.