Assessing the impact of child/adult differences in hepatic first-pass effect on the human kinetic adjustment factor for ingested toxicants

Article ID	Journal	Published Year	Pages	File Type
5857692	Regulatory Toxicology and Pharmacology	2013	9 Pages	PDF

Abstract

âº The human kinetic adjustment factor (HKAF) is given a default value of 3.2. âº For ingestion exposure, first-pass effect (FPE) is critically important. âº Stochastic steady-state equations reflecting FPE in children and adults were used. âº HKAF was computed as per an IPCS/WHO approach for ingested CYP1A2/2E1 substrates. âº HKAFs were lower or greater than 3.2, depending of the substrate's characteristics.

Keywords

CSAF CVSS Ing PBTK EAD MSP VOC CyP IPCs GST ADH RFC GSD RfD Vmax BSA FPE Body height Risk assessment Alcohol dehydrogenase geometric standard deviation standard deviation First-pass effect International Programme on Chemical Safety Cardiac output Volatile organic compound Interindividual variability Liver blood flow RAM, Random Access Memory, Read-Write Memory Michaelis–Menten constant Reference dose days Monte Carlo hours years body surface area cytochrome P-450 Monte-Carlo simulations Reference concentration chemical-specific adjustment factor Oral exposure IVF months body weight Intrinsic clearance CASS Clint glutathione-S-transferase