Evaluation of simple in vitro to in vivo extrapolation approaches for environmental compounds.
As part of an effort to support in silico/in vitro based risk assessment, we evaluated the accuracy associated with conducting simple in vitro to in vivo extrapolation (IVIVE) for environmental compounds using available in vitro human metabolism data. The IVIVE approach was applied to a number of compounds with a wide range of properties spanning the diversity of characteristics of environmental compounds, and where possible the resulting estimates of the in vivo steady-state blood concentration were compared with estimates derived on the basis of human in vivo kinetic data. There appears to be a systematic bias in the estimation of intrinsic clearance (Clint) from in vitro versus in vivo data, with in vitro based estimates underestimating in vivo clearance for small values of Clint but with the opposite relationship at large values of Clint. Nevertheless, the resulting estimates of Css were in good agreement. The chief drawback of the simple approach used in this study, which performs the IVIVE prediction for the parent compound only, is that it is not applicable for toxicity associated with a metabolite.
The Hamner Institutes for Health Sciences, NC, USA. Electronic address: myoon@thehamner.org.
Miyoung
M
Yoon
The Hamner Institutes for Health Sciences, NC, USA.
Alina
A
Efremenko
Institute for Risk Assessment Sciences, Division of Toxicology, University of Utrecht, NL, Netherlands.
Bas J
BJ
Blaauboer
The Hamner Institutes for Health Sciences, NC, USA.
Harvey J
HJ
Clewell
D000284:Administration, Oral; D000465:Algorithms; D000818:Animals; D003198:Computer Simulation; D003627:Data Interpretation, Statistical; D023381:Endpoint Determination; D004785:Environmental Pollutants / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity*; D005740:Gases; D006801:Humans; D019570:Inhalation Exposure; D008657:Metabolic Clearance Rate; D010599:Pharmacokinetics
D004785:Environmental Pollutants; D005740:Gases
C(ss); IVIVE; In vitro metabolism; Reverse dosimetry