Mixed LOF

Additional toxicological data

Administrative data

Endpoint:

additional toxicological information

Type of information:

other: PBPK Model

Reliability:

2 (reliable with restrictions)

Data source

Reference

Reference Type:

publication

Title:

Physiologically Based Pharmacokinetic Modeling of Cyclohexane as a Tool for
Integrating Animal and Human Test Data

Author:

Hissink, M, B. M. Kulig, J. Kruse, A. P. Freidig, M. Verwei, H. Muijser, J. H. C. M. Lammers, R. H. McKee, D. E. Owen, L. M. Sweeney, and F. Salmon

Year:

2009

Bibliographic source:

International Journal of Toxicology. 28(6) 498-509

Results and discussion

Any other information on results incl. tables

The publication describes a physiologically based pharmacokinetic model for cyclohexane (C6) and its use in comparing internal doses in rats and human volunteers following inhalation exposures.

“Parameters describing saturable metabolism of cyclohexane are measured in rats and used along with experimentally determined partition coefficients. The model is evaluated by comparing predicted blood and brain concentrations to data from studies in rats and then allometrically scaling the results to humans. Levels of cyclohexane in blood and exhaled air are measured in human volunteers and compared with model values. The model predicts that exposure of volunteers to cyclohexane at levels of 4100 mg/m3 (~1200 ppm) will result in brain levels similar to those in rats exposed to 8000 mg/m3 (the no-effect level for acute central nervous system effects). There are no acute central nervous system effects in humans exposed to 860 mg/m3...”